B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 anti...B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody screening.Micro-positron emission tomography(PET)imaging,biodistribution and pharmacokinetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission computed tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in vivo.Fu rthermore,the pharmacodynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models.Micro-PET imaging and biodistribution analysis with a gamma counter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid varied.The PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity.Interestingly,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor growth.Taken together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effective antitumor effects with an ideal safety profile.Therefore,we expect hu4G4 to be an excellent antibody for the development of GBM RIT.展开更多
AIM To observe the therapeutic effects and toxic side reactions of 125 I labeled hourse anti human AFP polyclonal antibodies in immuno targeting therapy against hepatocellular carcinoma (HCC).
AIM： To evaluate the multi-step pretargeting radioimmunoimaging （RII） and radioimmunotherapy （RTT） in nude mice bearing human colon carcinoma with avidin-biotin system labeled with 153^Sm. METHODS： Two- and thre...AIM： To evaluate the multi-step pretargeting radioimmunoimaging （RII） and radioimmunotherapy （RTT） in nude mice bearing human colon carcinoma with avidin-biotin system labeled with 153^Sm. METHODS： Two- and three-step strategies for avidinbiotin system pretargeting techniques were established. In a three-step procedure, human colon carcinoma bearing nude mice were first injected with biotinylated monoclonal antibody （McAb-Bt） followed by cold avidin （Av） 48 h later and then 153^Sm-DB2 24 h thereafter; whereas the twostep procedure consisted of injection of 153^Sm-SA 48 h after pretargeting with biotinylated anti-CEA monoclonal antibody （CEA McAb-Bt）. SPECT imaging and biodistribution were performed at 4, 24, 48, or 72 h after injection of 153^Sm-labeled compounds. Five groups of nude mice subcutaneously grafted with human colon carcinoma were treated 3 d after grafting. One group received the injection with 100 μg CEA McAb-Bt followed by cold avidin （80 μg） after 2 d and 11.1 MBCl I53Sm-DB2 after 1 d. Four control groups were treated respectively with 11.1 MBq 153^Sm- CEA McAb, ii.i MBq 153^Sm-nmIgG, ii.i MBq 153^Sm-DB2, 100 μL normal saline. Toxicity was evaluated by changes of leukocyte count, and the efficacy by variation in tumor volume. Histological analyses of tumors were performed. RESULTS： The three-step procedure allowed faster blood clearance and yielded higher tumor blood ratios （5.76 at 4 h and 12.94 at 24 h） of the 153^Sm-DB2. The tumor was clearly visualized at 4 h in y-imaging after the injection of 153^Sm-DB2, while a significant accumulation of 153^Sm-SA in the tumor was observed only 24 h after the injection and tumor blood ratios at 4 and 24 h were 1.00 and 2.03, respectively, in the two-step procedure. Pretargeting RIT and 153^Sm-CEA McAb had a strong tumor-inhibiting effect.The tumor inhibitory rate was 80.67% and 78.44%, respectively, five weeks after therapy. Histopathological evidence also indicated radioactive damage in tumor tissues as necrosis of tumor cells, while in the other organs such as liver and kidney no radioactive damage was observed. Leukocyte counts showed significant decrease after treatment in groups of 153^Sm-CEA McAb and 153^Sm- nmIgG. CONCLUSION： The two kinds of pretargeting strategies can elevate the target-to-nontarget ratio, decrease the blood background and shorten the imaging time compared to 153^Sm-CEA McAb. Three-step pretargeting RIT is as effident as 153^Sm-CEA McAb, but markedly less toxic. This study provides experimental evidence for the clinical application of pretargeting RII and RIT.展开更多
AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)wa...AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeledbiotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg) followed by intravenous injection of cold avidin (80 μg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.RESULTS: Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA Mc Ab-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the nontreated group, treated groups with and without avidin chase showed significant anti-tumor effects.CONCLUSION: Avidin chase can effectively reduce the side effects of RIT, and improve therapeutic efficacy.展开更多
Objective： Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized ~77Lutetium （177Lu）-trastuzumabiron ox...Objective： Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized ~77Lutetium （177Lu）-trastuzumabiron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging （MRI）. Methods： ^177Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield, nanoparticle size determination, stability in buffer and blood serum up to 4 d, immunoreactivity and biodistribution in normal mice were determined. In mice bearing breast tumor, liver and tumor activities were calculated with three methods： single photon emission computed tomography （SPECT）, MRI and organ extraction, which were compared with each other. Results： The good results of quality control tests （labeling yield： 61%±2%, mean nanoparticle hydrodynamic size： 41±15 nm, stability in buffer： 86%±5%, stability in blood serum： 80%±3%, immunoreactivity： 80%±2%） indicated that ^177Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor. Results showed that ^177Lu-trastuzumab-iron oxide nanoparticles with MRI had the ability to measure organ activities more accurate than SPECT. Conclusions： Co-conjugating radiopharmaceutical to MRI contrast agents such as iron oxide nanoparticles may be a good way for better dosimetry in nuclear medicine treatment.展开更多
Radiotherapy(RT)is a widely used way for cancer treatment.However,the efficiency of RT may come with various challenges such as low specificity,limitation by resistance,high dose and so on.Nitric oxide(NO)is known a v...Radiotherapy(RT)is a widely used way for cancer treatment.However,the efficiency of RT may come with various challenges such as low specificity,limitation by resistance,high dose and so on.Nitric oxide(NO)is known a very effective radiosensitizer of hypoxic tumor.However,NO cannot circulate in body with high concentration.Herein,an NIR light-responsive NO delivery system is developed for controlled and precisely release of NO to hypoxic tumors during radiotherapy.Tert-Butyl nitrite,which is an efficient NO source,is coupled to Ag2S quantum dots(QDs).NO could be generated and released from the Ag2S QDs effectively under the NIR irradiation due to the thermal effect.In addition,Ag is also a type of heavy metal that can benefit the RT therapy.We demonstrate that Ag2S NO delivery platforms remarkably maximize radiotherapy effects to inhibit tumor growth in CT26 tumor model.Furthermore,immunosuppressive tumor microenvironment is improved by our NO delivery system,significantly enhancing the anti-PD-L1 immune checkpoint blockade therapy.100% survival rate is achieved by the radio-immune combined therapy strategy based on the Ag2S NO delivery platforms.Our results suggest the promise of Ag2S NO delivery platforms for multifunctional cancer radioimmunotherapy.展开更多
AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer model.METHODS Phosphorylation of Akt, m TOR, the downstrea...AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer model.METHODS Phosphorylation of Akt, m TOR, the downstream effectors eukaryotic initiation factor 4 E binding protein 1(4 EBP1) and S6 ribosomal protein(S6) were evaluated in Bx PC-3 human pancreatic cancer cells treated with Yttrium-^(90)(^(90) Y) labeled anti-integrin α6β4 antibody(ITGA6 B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing Bx PC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses(cell proliferation marker Ki-67, DNA damage marker p-H2 AX and p-4 EBP1 staining) of tumors were performed for evaluation of combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235, or each arm alone.RESULTS We found that phosphorylation of Akt(p-Akt), 4 EBP1(p-4 EBP1) and S6(p-S6) was inhibited by BEZ235. Colony formation in Bx PC-3 cells was additively suppressed by the combination of ^(90) Y-ITGA6 B4 and BEZ235. Pretreatment with BEZ235 before ^(90) Y-ITGA6 B4 exposure resulted in significant reduction of cells plating efficiency(PE)(0.54 ± 0.11 vs 2.81 ± 0.14 with 185 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01; 0.39 ± 0.08 vs 1.88 ± 0.09 with 370 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01) when 5 × 10~3 cells per dish were plated. In vivo, the combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the ^(90) Y-ITGA6 B4 single injection treatment(1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P < 0.05), and for 41 d when compared with the BEZ235 treatment alone(1.8 ± 0.7 vs 3.14 ± 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, decreased Ki-67-positive cells, increased p-H2 AX-positive cells and decreased p-4 EBP1 expression. CONCLUSION The therapeutic efficacy of ^(90) Y-ITGA6 B4-RIT can be improved by combining with dual PI3 K and m TOR inhibitor, BEZ235, in a pancreatic cancer model suggesting potential clinical application.展开更多
Forty-three patients with surgically verified unresectable hepatoma had been treated by radioimmunotherapy(RIT)using￣(131)I antiferritin antibidy as a part of multimodality treatment during 1985 - 1990.The shortand l...Forty-three patients with surgically verified unresectable hepatoma had been treated by radioimmunotherapy(RIT)using￣(131)I antiferritin antibidy as a part of multimodality treatment during 1985 - 1990.The shortand long-term responses were compared with those in control group of 39 patients with unresectable hepatoma receiving conventional multimodality treatment in the same period.The rates of the tumor shrinkage,serum AFP decline and sequence resction were 67. 4% (29/43),69.6%(16/23)and 30.2%(13/43)respectively,which were significantly higher than those in contrul group[23.1%(15/39),40.0%(8/20)and 10.3%(4/39),respectively].The 1-,3- and 5-year survival rates were 61.5%,40.4%and 35.4%,respectively,for the RIT group,and 51.2%,20.1% and 15.5% ,respectrely,for the control group.The tumor size,dose of RIT and sequence resection were identified as significant factors (P=0.005,0.025 and 0.006,respectively, with Cox analysis model in 13 influencing factors.The results indicate that RIT was an effective one in multimodality treatment,particularly in the conversion of unresectable to resectable tumor.展开更多
Thirtytwo patients with surgically verified unresectable table hepatocellular carcinoma (HCC) have been treated by radioimmunotherapy (RIT) using intrahepatic arterial administration of￣(131)I anti HCC monoclonal ant...Thirtytwo patients with surgically verified unresectable table hepatocellular carcinoma (HCC) have been treated by radioimmunotherapy (RIT) using intrahepatic arterial administration of￣(131)I anti HCC monoclonal antibody (Hepama1) combined with hepetic artery ligation. Twenty of them had abnormal serum alpha fetoprotein (AFP,>20 ng/ml). Single photon emission computed tomography (SPECT) scan and quantitative assay of AFP were performed after RIT. The results revealed that when the tumor to liver ratio (T/L) was higher than 3.5 (Group A , n =3) , the serum AFP level declined markedly and then kept in stable for a tongtime; when the T/L ratio was less than 1.2 (Group C ,n=5), the serum AFP level did not change evidently within 2 months postinfusion; while the T/L ratio was between 1. 2 3. 5 (Group B, n= 12) , the serum AFP level increased transiently and then decreased within 2 4 weeks postinfusion. Sequentiat resection was achieved in all of the 3 patients of Group A, in 6 patients (50%) of Group B, and none in Group C. The correlation of serum AFP and effective treatment demonstrates the usefulness of this oncofetal protein marker as an indicator of neoplastic activity for HCC and T/L ratio might be a good indicator to predict tumor response to RIT in patients with展开更多
Factors influencing the therapeutic effect of radiolmmunotherapy with 131I labeled anti- human hepa-tocellular carcinoma (HCC) ferritin antibody (131I -FtAb) on thirty three patients with surgically proven unresectabl...Factors influencing the therapeutic effect of radiolmmunotherapy with 131I labeled anti- human hepa-tocellular carcinoma (HCC) ferritin antibody (131I -FtAb) on thirty three patients with surgically proven unresectable HCC were studied. Multi- variable analysis with Cox' s regression model revealed that the statistically sig-nifieant factors include tumor size, activity of 131I administered each time and the second-look resection. Survival of patients with tumor diameter less than 10 cm was higher than that of patients with tumor diameter more than 10 cm (1-year survival; 84% versus 50%) 3-year survival; 63% versus 9% ). Patients administered with 5. 55×108 Bq to 9. 25× 10(?) of 131I-FtAb each time yielded better effect than those administered with more than 9. 25×108 Bq of 131I -FtAb (1-year, survival: 86% ver- sus 55%; 3-year survival: 50% versus 18%). When tumor shrank, patients underwent second-look resection had a higher survival than those without receiving second- look resection (1- year survival, 80%versus 66 %; 3-year survival; 80% versus 11%).展开更多
The therapeutic efficacy of radioimmunotherapy against triple negative breast cancer(TNBC)is largely limited by the complicated tumor microenvironment(TME)and its immunosuppressive state.Thus developing a strategy to ...The therapeutic efficacy of radioimmunotherapy against triple negative breast cancer(TNBC)is largely limited by the complicated tumor microenvironment(TME)and its immunosuppressive state.Thus developing a strategy to reshape TME is expected to achieve highly efficient radioimmunotherapy.Therefore,we designed and synthesized a tellurium(Te)-driven maple leaf manganese carbonate nanotherapeutics(MnCO3@Te)by gas diffusion method,but also provided a chemical catalytic strategy in situ to augment ROS level and activate immune cells for improving cancer radioimmunotherapy.As expected,with the help of H2O2 in TEM,MnCO3@Te heterostructure with reversible Mn3+/Mn2+transition could catalyze the intracellular ROS overproduction to amplify radiotherapy.In addition,by virtue of the ability to scavenge H+in TME by carbonate group,MnCO3@Te directly promote the maturation of dendritic cells and macrophage M1 repolarization by stimulator of interferon genes(STING)pathway activation,resulting in remodeling immuno-microenvironment.As a result,MnCO3@Te synergized with radiotherapy and immune checkpoint blockade therapy effectively inhibited the breast cancer growth and lung metastasis in vivo.Collectively,these findings indicate that MnCO3@Te as an agonist,successfully overcome radioresistance and awaken immune systems,showing promising potential for solid tumor radioimmunotherapy.展开更多
Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacl...Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacles include insufficient antigen loading and off-target to DCs remain to their success.Here,we developed an imageable therapeutic vaccine with whole-antigen loading and target delivery constructed by ovalbumin(OVA)-biomineralized Bi_(2)S_(3) nanoparticles-pulsed DCs.Relying on the strong X-ray absorption and fluorescence labeling performance of Bi_(2)S_(3)@OVA nanoparticles,the in vivo spatiotemporal fate of the vaccine(Bi_(2)S_(3)@OVA@DC)can be noninvasively monitored by computed tomography and near-infrared fluorescence imaging in real time.The Bi_(2)S_(3)@OVA@DC can rapidly and durably accumulate in draining lymph nodes and thus trigger stronger T-cell responses compared to OVA-pulsed DCs.Meanwhile,Bi_(2)S_(3)@OVA@DC can further achieve in vivo antitumor effects against OVA-expressing B16F10 melanoma when combined with fractionated radiotherapy,resulting from the upregulation of cytotoxic CD8^(+)T cells and restraint of regulatory T cells in the tumor microenvironment,and the systemical secretion of OVA-specific IgG1/IgG2α antibody.Overall,we successfully fabricated an engineered DC vaccine featured in high whole-antigen loading capacity that can be precisely delivered to the lymphatic system for visualization,serving as a powerful therapeutic platform for cancer radioimmunotherapy.展开更多
OBJECTIVE: To assess the efficacy of fractionated administration of radiolabeled monoclonal antibody in the treatment of metastases after tumor volume reduction surgery, various experimental therapies were studied com...OBJECTIVE: To assess the efficacy of fractionated administration of radiolabeled monoclonal antibody in the treatment of metastases after tumor volume reduction surgery, various experimental therapies were studied comparatively. METHODS: A total of 200 inbred mice received tumor implantation from a murine adenocarcinoma cell line. The mice were randomly grouped to give saline, Arc-a, 131I-C50 in single or fractionated doses, cold C50, or non-specific 131I-IgG with or without surgical removal of the implanted tumor xenograft. RESULTS: In comparison to controls, animals receiving Arc-a and radioactive agents had longer survival, smaller tumor, better clinical condition, and less metastases foci. The best therapeutic response was noted after fractionated doses of 131I-C50, which showed better results in every aspect than those treated with other modalities. The favorable outcome was even more pronounced after tumor volume reduction. CONCLUSIONS: Fractionated dosing may improve the deposition of radiolabeled monoclonal antibody (McAb) and provide the best therapeutic effect on implanted tumor and metastases. Thus fractionated radioimmunotherapy (RIT) after tumor volume reduction might be a practical method with promising therapeutic results.展开更多
AIM:To investigate the safety and effectiveness of combined131I-metuximab and transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).METHODS:One hundred and eighty-five patients(159men and 26 ...AIM:To investigate the safety and effectiveness of combined131I-metuximab and transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).METHODS:One hundred and eighty-five patients(159men and 26 women)with advanced HCC were enrolled in this study from February 2009 to July 2011.There were 95 patients in the combined metuximab and TACE group,and 90 patients in the TACE only group.The patients were followed for 12 mo.Clinical symptoms,blood cell counts,Karnofsky Performance Score(KPS)evaluation and therapeutic effects according to the Response Evaluation Criteria in Solid Tumors were recorded and evaluated.RESULTS:The 1-mo effective rates(complete response+partial response+stable disease)of the test group and control group were 71.23%and 38.89%,respectively(P<0.001).The 6-,9-and 12-mo survival rates were 86.42%,74.07%and 60.49%for the test group and 60.0%,42.22%and 34.44%for the control group(P<0.001).The incidence of adverse events(gastrointestinal symptoms,fever and pain)and blood cell toxicity were significantly higher for the test group than for the control group(P<0.001).No severe131Imetuximab-related complications were identified.With respect to efficacy,patients in the test group had greater improvement in tumor-related pain(P=0.014)and increase in KPS(P<0.001)than those in the control group.CONCLUSION:Combination of131I-metuximab and TACE prolonged the survival time in patients with HCC compared with TACE alone.The combination treatment was safe and effective.展开更多
IM To study the radioimmunoimaging (RAII) using the human/mouse chimeric Ab to evaluate its targeting activity in animal models.METHODS To chimeric Ab was labeled with 131I. RAII was performed at different intervals...IM To study the radioimmunoimaging (RAII) using the human/mouse chimeric Ab to evaluate its targeting activity in animal models.METHODS To chimeric Ab was labeled with 131I. RAII was performed at different intervals after injection of radiolabeled Abs in nude mice with human hepatoma xenograft, and tissue distribution of radioactivity was measured. Comparison was made in the chimeric Ab between the single segment Ab and previous murine mAb against HBxAg.RESULTS The experimental objects developed tumorpositive image after 2 days of radiolabeled Abs injection, and the peak accumulation of radioactivity fell on the 7th day. The tumor/liver ratioactivity of the chimeric Ab, single segment Ab, antiHBx mAb, and the control group was 281±021, 244±016, 460±019, and 096±014, respectively.CONCLUSION The genetic engineering Abs have a considerable targeting activity which can be used as a novel humanized vector in the targeting treatment of liver cancer..展开更多
The improved tumoricidal effect of the radioatibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic...The improved tumoricidal effect of the radioatibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic efficacy of a monoclonal atibody (MAb) cocktail against human hepatocellular carcinoma. Therapeutic efficacy was determined by measuring the change in tumor size over a period, determining the percentage of growth inhibition of each treatment at various times after radioantibody therapy. boioimmunotherapy of SMMC-7721 human hepatoma xenografts in athymic nude mice with combination of 131I labeled Hepama-1 and 131Llabeled 9403 mouse MAbs was more effective than using either Hepeam-1 or 9403 Mab alone The MAb cocktail could target a greater number of hepstoma cells and increase the magnitude of hepatoma cen uptde of radioamibodies. The in vjtro results explain the enhanced effect of the MAb cocktail in in vjvo model system.展开更多
Despite unquestionable progress has been made inresection of small and large hepatocellular carcinoma'(HCC),the dismal outcome of unresectable HCC remains a great challenge.Fortunately,the progress of multidiscipl...Despite unquestionable progress has been made inresection of small and large hepatocellular carcinoma'(HCC),the dismal outcome of unresectable HCC remains a great challenge.Fortunately,the progress of multidisciplinary approach,particularly with new treatment modalities,has provided a new hope for unresectable HCC.This paper reports 477 patients with surgically verified unresectable HCC treated by different modalities, sequential resection was done in 55 patients(11.5%)due to marked shrinkage of the tumor.Patients treated with hepatic artery ligation(HAL),cannulation with infusion (HAI)and plus intraarterial targeting therapy(131I-antiHCC Ferritin IgG,131I-antiHCC monoclonal antibody,or 131I-Lipiodol)has higher sequential resection rate(33. 0%,31/94)when compared with other combination treatment(HAL+HAI,HAL+HAI+radiotherapy,11.7% ,22/188),and single treatment group(Cryosurgery,HAL,or HAI,1.0%,2/195). The combination of targeting therapy played an important role to the increasing number of sequential resection during 1978 through 1992.The 5-year survival of the 55 patients with sequential resection was as nigh as 60.8%.By the end of June 1993,13 patients survived more than 5 years, the longest being 15 years.展开更多
I-labeled anti-CEA monoclonal antibody injected intrasplenically has better effects on inhibiting liver metastasis from human colonic adenocarcinoma than that through tail vein in nu/nu mice model.
Monoclonal antibodies （MAbs） are a relatively new innovation in cancer treatment. At present, some monoclonal antibodies have increased the efficacy of the treatment of certain tumors with acceptable safety profiles...Monoclonal antibodies （MAbs） are a relatively new innovation in cancer treatment. At present, some monoclonal antibodies have increased the efficacy of the treatment of certain tumors with acceptable safety profiles. When monoclonal antibodies enter the body and attach to cancer cells, they function in several different ways： first, they can trigger the immune system to attack and kill that cancer cell; second, they can block the growth signals; third, they can prevent the formation of new blood vessels. Some naked MAbs such as rituximab can be directed to attach to the surface of cancer cells and make them easier for the immune system to find and destroy. The ability to produce antibodies with limited immunogeni-city has led to the production and testing of a host of agents, several of which have demonstrated clinically important antitumor activity and have received U.S. Food ＆ Drug Administration （FDA） approval as cancer treatments. To reduce the immunogenicity of murine anti- bodies, murine molecules are engineered to remove the immuno- genic content and to increase their immunologic efficiency. Radiolabeled antibodies composed of antibodies conjugated to radionuclides show efficacy in non-Hodgkin＇s lymphoma. Anti-vascular endothelial growth factor （VEGF） antibodies such as bevacizumab intercept the VEGF signal of tumors, thereby stopping them from connecting with their targets and blocking tumor growth. Trifunctional antibodies have revealed a new perspective in cancer therapy extending beyond primary destruction of tumor cells.展开更多
基金funded by the National Natural Science Foundation of China(31320103918 and 82104318)Key Research and Development Program of Jiangsu Province(BE2021644)+4 种基金the Jiangsu Innovative and Entrepreneurial Talent Programme(JSSCBS20211568)the Science and Technology Plan of Suzhou(SKJYD2021161 and SKY2022046)Key Project of Jiangsu Provincial Health Commission(zd2021050)the Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University(GZK1202203)support of Jiangsu Institute of Nuclear Medicine for the ^(89)Zr-PET imaging in this study。
文摘B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody screening.Micro-positron emission tomography(PET)imaging,biodistribution and pharmacokinetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission computed tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in vivo.Fu rthermore,the pharmacodynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models.Micro-PET imaging and biodistribution analysis with a gamma counter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid varied.The PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity.Interestingly,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor growth.Taken together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effective antitumor effects with an ideal safety profile.Therefore,we expect hu4G4 to be an excellent antibody for the development of GBM RIT.
文摘AIM To observe the therapeutic effects and toxic side reactions of 125 I labeled hourse anti human AFP polyclonal antibodies in immuno targeting therapy against hepatocellular carcinoma (HCC).
文摘AIM： To evaluate the multi-step pretargeting radioimmunoimaging （RII） and radioimmunotherapy （RTT） in nude mice bearing human colon carcinoma with avidin-biotin system labeled with 153^Sm. METHODS： Two- and three-step strategies for avidinbiotin system pretargeting techniques were established. In a three-step procedure, human colon carcinoma bearing nude mice were first injected with biotinylated monoclonal antibody （McAb-Bt） followed by cold avidin （Av） 48 h later and then 153^Sm-DB2 24 h thereafter; whereas the twostep procedure consisted of injection of 153^Sm-SA 48 h after pretargeting with biotinylated anti-CEA monoclonal antibody （CEA McAb-Bt）. SPECT imaging and biodistribution were performed at 4, 24, 48, or 72 h after injection of 153^Sm-labeled compounds. Five groups of nude mice subcutaneously grafted with human colon carcinoma were treated 3 d after grafting. One group received the injection with 100 μg CEA McAb-Bt followed by cold avidin （80 μg） after 2 d and 11.1 MBCl I53Sm-DB2 after 1 d. Four control groups were treated respectively with 11.1 MBq 153^Sm- CEA McAb, ii.i MBq 153^Sm-nmIgG, ii.i MBq 153^Sm-DB2, 100 μL normal saline. Toxicity was evaluated by changes of leukocyte count, and the efficacy by variation in tumor volume. Histological analyses of tumors were performed. RESULTS： The three-step procedure allowed faster blood clearance and yielded higher tumor blood ratios （5.76 at 4 h and 12.94 at 24 h） of the 153^Sm-DB2. The tumor was clearly visualized at 4 h in y-imaging after the injection of 153^Sm-DB2, while a significant accumulation of 153^Sm-SA in the tumor was observed only 24 h after the injection and tumor blood ratios at 4 and 24 h were 1.00 and 2.03, respectively, in the two-step procedure. Pretargeting RIT and 153^Sm-CEA McAb had a strong tumor-inhibiting effect.The tumor inhibitory rate was 80.67% and 78.44%, respectively, five weeks after therapy. Histopathological evidence also indicated radioactive damage in tumor tissues as necrosis of tumor cells, while in the other organs such as liver and kidney no radioactive damage was observed. Leukocyte counts showed significant decrease after treatment in groups of 153^Sm-CEA McAb and 153^Sm- nmIgG. CONCLUSION： The two kinds of pretargeting strategies can elevate the target-to-nontarget ratio, decrease the blood background and shorten the imaging time compared to 153^Sm-CEA McAb. Three-step pretargeting RIT is as effident as 153^Sm-CEA McAb, but markedly less toxic. This study provides experimental evidence for the clinical application of pretargeting RII and RIT.
基金Supported by the China Postdoctoral Science Foundation, No. 2003033345Medical Sciences and Technology Foundation of Guangdong Province, No.A2000389
文摘AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeledbiotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg) followed by intravenous injection of cold avidin (80 μg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.RESULTS: Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA Mc Ab-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the nontreated group, treated groups with and without avidin chase showed significant anti-tumor effects.CONCLUSION: Avidin chase can effectively reduce the side effects of RIT, and improve therapeutic efficacy.
文摘Objective： Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized ~77Lutetium （177Lu）-trastuzumabiron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging （MRI）. Methods： ^177Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield, nanoparticle size determination, stability in buffer and blood serum up to 4 d, immunoreactivity and biodistribution in normal mice were determined. In mice bearing breast tumor, liver and tumor activities were calculated with three methods： single photon emission computed tomography （SPECT）, MRI and organ extraction, which were compared with each other. Results： The good results of quality control tests （labeling yield： 61%±2%, mean nanoparticle hydrodynamic size： 41±15 nm, stability in buffer： 86%±5%, stability in blood serum： 80%±3%, immunoreactivity： 80%±2%） indicated that ^177Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor. Results showed that ^177Lu-trastuzumab-iron oxide nanoparticles with MRI had the ability to measure organ activities more accurate than SPECT. Conclusions： Co-conjugating radiopharmaceutical to MRI contrast agents such as iron oxide nanoparticles may be a good way for better dosimetry in nuclear medicine treatment.
基金This work is supported by grants from startup supports of Soochow University and the Program for Jiangsu Specially Appointed Professors to C.WThis work is partly supported by Collaborative Innovation Center of Suzhou Nano Science&Technology,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the 111 Project+2 种基金This work was also supported by the National Natural Science Foundation of China(No.31900988)the Natural Science Foundation of Jiangsu Province(No.SBK2019040088)Jiangsu Province Six Talent Peaks Project(No.SWYY-110).
文摘Radiotherapy(RT)is a widely used way for cancer treatment.However,the efficiency of RT may come with various challenges such as low specificity,limitation by resistance,high dose and so on.Nitric oxide(NO)is known a very effective radiosensitizer of hypoxic tumor.However,NO cannot circulate in body with high concentration.Herein,an NIR light-responsive NO delivery system is developed for controlled and precisely release of NO to hypoxic tumors during radiotherapy.Tert-Butyl nitrite,which is an efficient NO source,is coupled to Ag2S quantum dots(QDs).NO could be generated and released from the Ag2S QDs effectively under the NIR irradiation due to the thermal effect.In addition,Ag is also a type of heavy metal that can benefit the RT therapy.We demonstrate that Ag2S NO delivery platforms remarkably maximize radiotherapy effects to inhibit tumor growth in CT26 tumor model.Furthermore,immunosuppressive tumor microenvironment is improved by our NO delivery system,significantly enhancing the anti-PD-L1 immune checkpoint blockade therapy.100% survival rate is achieved by the radio-immune combined therapy strategy based on the Ag2S NO delivery platforms.Our results suggest the promise of Ag2S NO delivery platforms for multifunctional cancer radioimmunotherapy.
基金Supported by(partially)a Grant-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science and Technology,Japan,No.17K10460 to Aung W
文摘AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer model.METHODS Phosphorylation of Akt, m TOR, the downstream effectors eukaryotic initiation factor 4 E binding protein 1(4 EBP1) and S6 ribosomal protein(S6) were evaluated in Bx PC-3 human pancreatic cancer cells treated with Yttrium-^(90)(^(90) Y) labeled anti-integrin α6β4 antibody(ITGA6 B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing Bx PC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses(cell proliferation marker Ki-67, DNA damage marker p-H2 AX and p-4 EBP1 staining) of tumors were performed for evaluation of combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235, or each arm alone.RESULTS We found that phosphorylation of Akt(p-Akt), 4 EBP1(p-4 EBP1) and S6(p-S6) was inhibited by BEZ235. Colony formation in Bx PC-3 cells was additively suppressed by the combination of ^(90) Y-ITGA6 B4 and BEZ235. Pretreatment with BEZ235 before ^(90) Y-ITGA6 B4 exposure resulted in significant reduction of cells plating efficiency(PE)(0.54 ± 0.11 vs 2.81 ± 0.14 with 185 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01; 0.39 ± 0.08 vs 1.88 ± 0.09 with 370 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01) when 5 × 10~3 cells per dish were plated. In vivo, the combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the ^(90) Y-ITGA6 B4 single injection treatment(1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P < 0.05), and for 41 d when compared with the BEZ235 treatment alone(1.8 ± 0.7 vs 3.14 ± 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, decreased Ki-67-positive cells, increased p-H2 AX-positive cells and decreased p-4 EBP1 expression. CONCLUSION The therapeutic efficacy of ^(90) Y-ITGA6 B4-RIT can be improved by combining with dual PI3 K and m TOR inhibitor, BEZ235, in a pancreatic cancer model suggesting potential clinical application.
文摘Forty-three patients with surgically verified unresectable hepatoma had been treated by radioimmunotherapy(RIT)using￣(131)I antiferritin antibidy as a part of multimodality treatment during 1985 - 1990.The shortand long-term responses were compared with those in control group of 39 patients with unresectable hepatoma receiving conventional multimodality treatment in the same period.The rates of the tumor shrinkage,serum AFP decline and sequence resction were 67. 4% (29/43),69.6%(16/23)and 30.2%(13/43)respectively,which were significantly higher than those in contrul group[23.1%(15/39),40.0%(8/20)and 10.3%(4/39),respectively].The 1-,3- and 5-year survival rates were 61.5%,40.4%and 35.4%,respectively,for the RIT group,and 51.2%,20.1% and 15.5% ,respectrely,for the control group.The tumor size,dose of RIT and sequence resection were identified as significant factors (P=0.005,0.025 and 0.006,respectively, with Cox analysis model in 13 influencing factors.The results indicate that RIT was an effective one in multimodality treatment,particularly in the conversion of unresectable to resectable tumor.
文摘Thirtytwo patients with surgically verified unresectable table hepatocellular carcinoma (HCC) have been treated by radioimmunotherapy (RIT) using intrahepatic arterial administration of￣(131)I anti HCC monoclonal antibody (Hepama1) combined with hepetic artery ligation. Twenty of them had abnormal serum alpha fetoprotein (AFP,>20 ng/ml). Single photon emission computed tomography (SPECT) scan and quantitative assay of AFP were performed after RIT. The results revealed that when the tumor to liver ratio (T/L) was higher than 3.5 (Group A , n =3) , the serum AFP level declined markedly and then kept in stable for a tongtime; when the T/L ratio was less than 1.2 (Group C ,n=5), the serum AFP level did not change evidently within 2 months postinfusion; while the T/L ratio was between 1. 2 3. 5 (Group B, n= 12) , the serum AFP level increased transiently and then decreased within 2 4 weeks postinfusion. Sequentiat resection was achieved in all of the 3 patients of Group A, in 6 patients (50%) of Group B, and none in Group C. The correlation of serum AFP and effective treatment demonstrates the usefulness of this oncofetal protein marker as an indicator of neoplastic activity for HCC and T/L ratio might be a good indicator to predict tumor response to RIT in patients with
文摘Factors influencing the therapeutic effect of radiolmmunotherapy with 131I labeled anti- human hepa-tocellular carcinoma (HCC) ferritin antibody (131I -FtAb) on thirty three patients with surgically proven unresectable HCC were studied. Multi- variable analysis with Cox' s regression model revealed that the statistically sig-nifieant factors include tumor size, activity of 131I administered each time and the second-look resection. Survival of patients with tumor diameter less than 10 cm was higher than that of patients with tumor diameter more than 10 cm (1-year survival; 84% versus 50%) 3-year survival; 63% versus 9% ). Patients administered with 5. 55×108 Bq to 9. 25× 10(?) of 131I-FtAb each time yielded better effect than those administered with more than 9. 25×108 Bq of 131I -FtAb (1-year, survival: 86% ver- sus 55%; 3-year survival: 50% versus 18%). When tumor shrank, patients underwent second-look resection had a higher survival than those without receiving second- look resection (1- year survival, 80%versus 66 %; 3-year survival; 80% versus 11%).
基金supported by National Science Fund for Distinguished Young Scholars(82225025)National Natural Science Foundation of China(21877049,32171296,32201166,82172088)+2 种基金Guangdong Natural Science Foundation(2020B1515120043)Guangdong Basic and Applied Basic Research Fund Project(No.2021A1515111027)K.C.Wong Education Foundation.
文摘The therapeutic efficacy of radioimmunotherapy against triple negative breast cancer(TNBC)is largely limited by the complicated tumor microenvironment(TME)and its immunosuppressive state.Thus developing a strategy to reshape TME is expected to achieve highly efficient radioimmunotherapy.Therefore,we designed and synthesized a tellurium(Te)-driven maple leaf manganese carbonate nanotherapeutics(MnCO3@Te)by gas diffusion method,but also provided a chemical catalytic strategy in situ to augment ROS level and activate immune cells for improving cancer radioimmunotherapy.As expected,with the help of H2O2 in TEM,MnCO3@Te heterostructure with reversible Mn3+/Mn2+transition could catalyze the intracellular ROS overproduction to amplify radiotherapy.In addition,by virtue of the ability to scavenge H+in TME by carbonate group,MnCO3@Te directly promote the maturation of dendritic cells and macrophage M1 repolarization by stimulator of interferon genes(STING)pathway activation,resulting in remodeling immuno-microenvironment.As a result,MnCO3@Te synergized with radiotherapy and immune checkpoint blockade therapy effectively inhibited the breast cancer growth and lung metastasis in vivo.Collectively,these findings indicate that MnCO3@Te as an agonist,successfully overcome radioresistance and awaken immune systems,showing promising potential for solid tumor radioimmunotherapy.
基金National Natural Science Foundation of China,Grant/Award Numbers:22122407,12175162,32171403,12075164,31971319,21874097National Key Research Program of China,Grant/Award Number:2018YFA0208800+1 种基金Tang Scholar ProgramScientific Research Program for Young Talents of China National Nuclear Corporation and A Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacles include insufficient antigen loading and off-target to DCs remain to their success.Here,we developed an imageable therapeutic vaccine with whole-antigen loading and target delivery constructed by ovalbumin(OVA)-biomineralized Bi_(2)S_(3) nanoparticles-pulsed DCs.Relying on the strong X-ray absorption and fluorescence labeling performance of Bi_(2)S_(3)@OVA nanoparticles,the in vivo spatiotemporal fate of the vaccine(Bi_(2)S_(3)@OVA@DC)can be noninvasively monitored by computed tomography and near-infrared fluorescence imaging in real time.The Bi_(2)S_(3)@OVA@DC can rapidly and durably accumulate in draining lymph nodes and thus trigger stronger T-cell responses compared to OVA-pulsed DCs.Meanwhile,Bi_(2)S_(3)@OVA@DC can further achieve in vivo antitumor effects against OVA-expressing B16F10 melanoma when combined with fractionated radiotherapy,resulting from the upregulation of cytotoxic CD8^(+)T cells and restraint of regulatory T cells in the tumor microenvironment,and the systemical secretion of OVA-specific IgG1/IgG2α antibody.Overall,we successfully fabricated an engineered DC vaccine featured in high whole-antigen loading capacity that can be precisely delivered to the lymphatic system for visualization,serving as a powerful therapeutic platform for cancer radioimmunotherapy.
文摘OBJECTIVE: To assess the efficacy of fractionated administration of radiolabeled monoclonal antibody in the treatment of metastases after tumor volume reduction surgery, various experimental therapies were studied comparatively. METHODS: A total of 200 inbred mice received tumor implantation from a murine adenocarcinoma cell line. The mice were randomly grouped to give saline, Arc-a, 131I-C50 in single or fractionated doses, cold C50, or non-specific 131I-IgG with or without surgical removal of the implanted tumor xenograft. RESULTS: In comparison to controls, animals receiving Arc-a and radioactive agents had longer survival, smaller tumor, better clinical condition, and less metastases foci. The best therapeutic response was noted after fractionated doses of 131I-C50, which showed better results in every aspect than those treated with other modalities. The favorable outcome was even more pronounced after tumor volume reduction. CONCLUSIONS: Fractionated dosing may improve the deposition of radiolabeled monoclonal antibody (McAb) and provide the best therapeutic effect on implanted tumor and metastases. Thus fractionated radioimmunotherapy (RIT) after tumor volume reduction might be a practical method with promising therapeutic results.
文摘AIM:To investigate the safety and effectiveness of combined131I-metuximab and transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).METHODS:One hundred and eighty-five patients(159men and 26 women)with advanced HCC were enrolled in this study from February 2009 to July 2011.There were 95 patients in the combined metuximab and TACE group,and 90 patients in the TACE only group.The patients were followed for 12 mo.Clinical symptoms,blood cell counts,Karnofsky Performance Score(KPS)evaluation and therapeutic effects according to the Response Evaluation Criteria in Solid Tumors were recorded and evaluated.RESULTS:The 1-mo effective rates(complete response+partial response+stable disease)of the test group and control group were 71.23%and 38.89%,respectively(P<0.001).The 6-,9-and 12-mo survival rates were 86.42%,74.07%and 60.49%for the test group and 60.0%,42.22%and 34.44%for the control group(P<0.001).The incidence of adverse events(gastrointestinal symptoms,fever and pain)and blood cell toxicity were significantly higher for the test group than for the control group(P<0.001).No severe131Imetuximab-related complications were identified.With respect to efficacy,patients in the test group had greater improvement in tumor-related pain(P=0.014)and increase in KPS(P<0.001)than those in the control group.CONCLUSION:Combination of131I-metuximab and TACE prolonged the survival time in patients with HCC compared with TACE alone.The combination treatment was safe and effective.
文摘IM To study the radioimmunoimaging (RAII) using the human/mouse chimeric Ab to evaluate its targeting activity in animal models.METHODS To chimeric Ab was labeled with 131I. RAII was performed at different intervals after injection of radiolabeled Abs in nude mice with human hepatoma xenograft, and tissue distribution of radioactivity was measured. Comparison was made in the chimeric Ab between the single segment Ab and previous murine mAb against HBxAg.RESULTS The experimental objects developed tumorpositive image after 2 days of radiolabeled Abs injection, and the peak accumulation of radioactivity fell on the 7th day. The tumor/liver ratioactivity of the chimeric Ab, single segment Ab, antiHBx mAb, and the control group was 281±021, 244±016, 460±019, and 096±014, respectively.CONCLUSION The genetic engineering Abs have a considerable targeting activity which can be used as a novel humanized vector in the targeting treatment of liver cancer..
文摘The improved tumoricidal effect of the radioatibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic efficacy of a monoclonal atibody (MAb) cocktail against human hepatocellular carcinoma. Therapeutic efficacy was determined by measuring the change in tumor size over a period, determining the percentage of growth inhibition of each treatment at various times after radioantibody therapy. boioimmunotherapy of SMMC-7721 human hepatoma xenografts in athymic nude mice with combination of 131I labeled Hepama-1 and 131Llabeled 9403 mouse MAbs was more effective than using either Hepeam-1 or 9403 Mab alone The MAb cocktail could target a greater number of hepstoma cells and increase the magnitude of hepatoma cen uptde of radioamibodies. The in vjtro results explain the enhanced effect of the MAb cocktail in in vjvo model system.
文摘Despite unquestionable progress has been made inresection of small and large hepatocellular carcinoma'(HCC),the dismal outcome of unresectable HCC remains a great challenge.Fortunately,the progress of multidisciplinary approach,particularly with new treatment modalities,has provided a new hope for unresectable HCC.This paper reports 477 patients with surgically verified unresectable HCC treated by different modalities, sequential resection was done in 55 patients(11.5%)due to marked shrinkage of the tumor.Patients treated with hepatic artery ligation(HAL),cannulation with infusion (HAI)and plus intraarterial targeting therapy(131I-antiHCC Ferritin IgG,131I-antiHCC monoclonal antibody,or 131I-Lipiodol)has higher sequential resection rate(33. 0%,31/94)when compared with other combination treatment(HAL+HAI,HAL+HAI+radiotherapy,11.7% ,22/188),and single treatment group(Cryosurgery,HAL,or HAI,1.0%,2/195). The combination of targeting therapy played an important role to the increasing number of sequential resection during 1978 through 1992.The 5-year survival of the 55 patients with sequential resection was as nigh as 60.8%.By the end of June 1993,13 patients survived more than 5 years, the longest being 15 years.
文摘I-labeled anti-CEA monoclonal antibody injected intrasplenically has better effects on inhibiting liver metastasis from human colonic adenocarcinoma than that through tail vein in nu/nu mice model.
基金This work was supported by grants from the National Natural Science Foundation of China （Grant nos. 30800561 and 31171303） and Tianjin Natural Science Foundation （Grant no. 09JCZDJC18100）.
文摘Monoclonal antibodies （MAbs） are a relatively new innovation in cancer treatment. At present, some monoclonal antibodies have increased the efficacy of the treatment of certain tumors with acceptable safety profiles. When monoclonal antibodies enter the body and attach to cancer cells, they function in several different ways： first, they can trigger the immune system to attack and kill that cancer cell; second, they can block the growth signals; third, they can prevent the formation of new blood vessels. Some naked MAbs such as rituximab can be directed to attach to the surface of cancer cells and make them easier for the immune system to find and destroy. The ability to produce antibodies with limited immunogeni-city has led to the production and testing of a host of agents, several of which have demonstrated clinically important antitumor activity and have received U.S. Food ＆ Drug Administration （FDA） approval as cancer treatments. To reduce the immunogenicity of murine anti- bodies, murine molecules are engineered to remove the immuno- genic content and to increase their immunologic efficiency. Radiolabeled antibodies composed of antibodies conjugated to radionuclides show efficacy in non-Hodgkin＇s lymphoma. Anti-vascular endothelial growth factor （VEGF） antibodies such as bevacizumab intercept the VEGF signal of tumors, thereby stopping them from connecting with their targets and blocking tumor growth. Trifunctional antibodies have revealed a new perspective in cancer therapy extending beyond primary destruction of tumor cells.
