The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimen...The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.展开更多
Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction.However,action recognition currently used in non-human primate(NHP)research ...Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction.However,action recognition currently used in non-human primate(NHP)research relies heavily on intense manual labor and lacks standardized assessment.In this work,we established two standard benchmark datasets of NHPs in the laboratory:Monkeyin Lab(Mi L),which includes 13 categories of actions and postures,and MiL2D,which includes sequences of two-dimensional(2D)skeleton features.Furthermore,based on recent methodological advances in deep learning and skeleton visualization,we introduced the Monkey Monitor Kit(Mon Kit)toolbox for automatic action recognition,posture estimation,and identification of fine motor activity in monkeys.Using the datasets and Mon Kit,we evaluated the daily behaviors of wild-type cynomolgus monkeys within their home cages and experimental environments and compared these observations with the behaviors exhibited by cynomolgus monkeys possessing mutations in the MECP2 gene as a disease model of Rett syndrome(RTT).Mon Kit was used to assess motor function,stereotyped behaviors,and depressive phenotypes,with the outcomes compared with human manual detection.Mon Kit established consistent criteria for identifying behavior in NHPs with high accuracy and efficiency,thus providing a novel and comprehensive tool for assessing phenotypic behavior in monkeys.展开更多
Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and ...Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.展开更多
CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))subpopulatio...CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))subpopulations.Inhibitor of DNA binding protein 2(Id2)has been shown to play important roles in T-cell development and CD8^(+)T-cell immunity.However,the role of Id2 in CD8^(+)T-cell exhaustion is unclear.Here,we found that Id2 transcriptionally and epigenetically regulates the generation of Texprog cells and their conversion to Texterm cells.Genetic deletion of Id2 dampens CD8^(+)T-cell-mediated immune responses and the maintenance of stem-like CD8^(+)T-cell subpopulations,suppresses PD-1 blockade and increases tumor susceptibility.Mechanistically,through its HLH domain,Id2 binds and disrupts the assembly of the Tcf3-Tal1 transcriptional regulatory complex,and thus modulates chromatin accessibility at the Slamf6 promoter by preventing the interaction of Tcf3 with the histone lysine demethylase LSD1.Therefore,Id2 increases the abundance of the permissive H3K4me2 mark on the Tcf3-occupied E-boxes in the Slamf6 promoter,modulates chromatin accessibility at the Slamf6 promoter and epigenetically regulates the generation of Slamf6+Texprog cells.An LSD1 inhibitor GSK2879552 can rescue the Id2 knockout phenotype in tumor-bearing mice.Inhibition of LSD1 increases the abundance of Slamf6^(+)Tim-3^(−)Tex^(prog) cells in tumors and the expression level of Tcf1 in Id2-deleted CD8+T cells.This study demonstrates that Id2-mediated transcriptional and epigenetic modification drives hierarchical CD8^(+)T-cell exhaustion,and the mechanistic insights gained may have implications for therapeutic intervention with tumor immune evasion.展开更多
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with a...Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma? Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.展开更多
Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising f...Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvlll) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvlll in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.展开更多
The abnormal activation of CD4^(+)CD45RO+memory T(Tm)cells plays an important role in the pathogenesis of rheumatoid arthritis(RA).Previous studies have shown that CD147 participates in T-cell activation.However,it re...The abnormal activation of CD4^(+)CD45RO+memory T(Tm)cells plays an important role in the pathogenesis of rheumatoid arthritis(RA).Previous studies have shown that CD147 participates in T-cell activation.However,it remains unclear whether CD147 is involved in abnormal Tm-cell activation in RA patients.In this study,we demonstrated that CD147 was predominantly upregulated in Tm cells derived from RA patients.The anti-CD147 mAb 5A12 specifically inhibited Tm-cell activation and proliferation and further restrained osteoclastogenesis.Using a structural–functional approach,we depicted the interface between 5A12 and CD147.This allowed us to identify two critical residues,Lys63 and Asp65,as potential targets for RA treatment,as the double mutation K63A/D65A inhibited Tm-cell activation,mimicking the neutralization by 5A12.This study provides not only a theoretical basis for a“CD147-Tm/Osteoclast-RA chain”for the potential prevention and treatment of RA or other T-cell-mediated autoimmune diseases but also a new target for related drug design and development.展开更多
Meplazumab is an anti-CD147 humanized IgG2 antibody.The purpose of this study was to characterize the nonclinical safety,tolerance and efficacy evaluation of meplazumab treating chloroquine resistant Plasmodium falcip...Meplazumab is an anti-CD147 humanized IgG2 antibody.The purpose of this study was to characterize the nonclinical safety,tolerance and efficacy evaluation of meplazumab treating chloroquine resistant Plasmodium falciparum.Meplazumab was well tolerated in repeat-dose toxicology studies in cynomolgus monkeys.No observed adverse effect level was 12 mg/kg.No difference between genders in the primary toxicokinetic parameters after repeat intravenous injection of meplazumab.No increased levels of drug exposure and drug accumulation were observed in different gender and dose groups.Meplazumab had a low cross-reactivity rate in various tissues and did not cause hemolysis or aggregation of red blood cells.The biodistribution and excretion results indicated that meplazumab was mainly distributed in the plasma,whole blood,and hemocytes,and excreted in the urine.Moreover,meplazumab effectively inhibited the parasites from invading erythrocytes in humanized mice in a time-dependent manner and the efficacy is superior to that of chloroquine.All these studies suggested that meplazumab is safe and well tolerated in cynomolgus monkeys,and effectively inhibits P.falciparum from invading into human red blood cells.These nonclinical data facilitated the initiation of an ongoing clinical trial of meplazumab for antimalarial therapy.展开更多
Cancer is a significant global health problem and remains one of the most challenging threats to human health. Conventional cancer treatments may include surgery, chemotherapy, radiation therapy, targeted therapy, and...Cancer is a significant global health problem and remains one of the most challenging threats to human health. Conventional cancer treatments may include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Immunotherapy is still considered as a highly exciting field for new discoveries and treatments for cancer [1]. Immunotherapy was cited by Science as one of the top 10 breakthroughs in the world in 2013.展开更多
基金Scientific and Technological Resources Coordination Project of Shaanxi Province,Grant/Award Number:2020PT-002,2022PT-43 and CX-PT-18Special Fund for Military Laboratory Animals,Grant/Award Number:SYDW_KY(2021)13State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Grant/Award Number:CBSKL2022ZZ28。
文摘The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.
基金supported by the National Key R&D Program of China (2021ZD0202805,2019YFA0709504,2021ZD0200900)National Defense Science and Technology Innovation Special Zone Spark Project (20-163-00-TS-009-152-01)+4 种基金National Natural Science Foundation of China (31900719,U20A20227,82125008)Innovative Research Team of High-level Local Universities in Shanghai,Science and Technology Committee Rising-Star Program (19QA1401400)111 Project (B18015)Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)Shanghai Center for Brain Science and Brain-Inspired Technology。
文摘Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction.However,action recognition currently used in non-human primate(NHP)research relies heavily on intense manual labor and lacks standardized assessment.In this work,we established two standard benchmark datasets of NHPs in the laboratory:Monkeyin Lab(Mi L),which includes 13 categories of actions and postures,and MiL2D,which includes sequences of two-dimensional(2D)skeleton features.Furthermore,based on recent methodological advances in deep learning and skeleton visualization,we introduced the Monkey Monitor Kit(Mon Kit)toolbox for automatic action recognition,posture estimation,and identification of fine motor activity in monkeys.Using the datasets and Mon Kit,we evaluated the daily behaviors of wild-type cynomolgus monkeys within their home cages and experimental environments and compared these observations with the behaviors exhibited by cynomolgus monkeys possessing mutations in the MECP2 gene as a disease model of Rett syndrome(RTT).Mon Kit was used to assess motor function,stereotyped behaviors,and depressive phenotypes,with the outcomes compared with human manual detection.Mon Kit established consistent criteria for identifying behavior in NHPs with high accuracy and efficiency,thus providing a novel and comprehensive tool for assessing phenotypic behavior in monkeys.
基金supported by the Science and Technology Project of Shaanxi Province,China(No.2021 PT-047,2022 PT-43,2022JQ-874)the Young Elite Scientist Sponsorship Program by Cast(China Association for Science andTechnology)(No.2020QNRC001).
文摘Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.
基金supported by the Major Program of the National Natural Science Foundation of China(No.82293635,No.92169211)the National Key Research and Development Program of China(No.2019YFC1316302,No.2023YFC2306400)+1 种基金the National Natural Science Foundation of China(No.81972711)supported by the Science Fund Program for Distinguished Young Scholars(LC).
文摘CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))subpopulations.Inhibitor of DNA binding protein 2(Id2)has been shown to play important roles in T-cell development and CD8^(+)T-cell immunity.However,the role of Id2 in CD8^(+)T-cell exhaustion is unclear.Here,we found that Id2 transcriptionally and epigenetically regulates the generation of Texprog cells and their conversion to Texterm cells.Genetic deletion of Id2 dampens CD8^(+)T-cell-mediated immune responses and the maintenance of stem-like CD8^(+)T-cell subpopulations,suppresses PD-1 blockade and increases tumor susceptibility.Mechanistically,through its HLH domain,Id2 binds and disrupts the assembly of the Tcf3-Tal1 transcriptional regulatory complex,and thus modulates chromatin accessibility at the Slamf6 promoter by preventing the interaction of Tcf3 with the histone lysine demethylase LSD1.Therefore,Id2 increases the abundance of the permissive H3K4me2 mark on the Tcf3-occupied E-boxes in the Slamf6 promoter,modulates chromatin accessibility at the Slamf6 promoter and epigenetically regulates the generation of Slamf6+Texprog cells.An LSD1 inhibitor GSK2879552 can rescue the Id2 knockout phenotype in tumor-bearing mice.Inhibition of LSD1 increases the abundance of Slamf6^(+)Tim-3^(−)Tex^(prog) cells in tumors and the expression level of Tcf1 in Id2-deleted CD8+T cells.This study demonstrates that Id2-mediated transcriptional and epigenetic modification drives hierarchical CD8^(+)T-cell exhaustion,and the mechanistic insights gained may have implications for therapeutic intervention with tumor immune evasion.
基金grants from the National Natural Science Foundation of China (Nos.31571434.81874155, and 81872482)the National Science and Technology Major Project (No.2015CB553701).
文摘Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma? Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.
文摘Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvlll) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvlll in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.
基金supported by grant(2015CB553704)from the National Basic Research Program of China,grants(2013ZX09301301 and 2014ZX09508002-002)+3 种基金from the National Science and Technology Major Project of China,grant(2017YFC0909002)from the National Key Research Project of China,grant(31470792)from the National Natural Science Foundation of China and grant(XDB08030102)from the Strategic Priority Research Program of the Chinese Academy of Sciences.
文摘The abnormal activation of CD4^(+)CD45RO+memory T(Tm)cells plays an important role in the pathogenesis of rheumatoid arthritis(RA).Previous studies have shown that CD147 participates in T-cell activation.However,it remains unclear whether CD147 is involved in abnormal Tm-cell activation in RA patients.In this study,we demonstrated that CD147 was predominantly upregulated in Tm cells derived from RA patients.The anti-CD147 mAb 5A12 specifically inhibited Tm-cell activation and proliferation and further restrained osteoclastogenesis.Using a structural–functional approach,we depicted the interface between 5A12 and CD147.This allowed us to identify two critical residues,Lys63 and Asp65,as potential targets for RA treatment,as the double mutation K63A/D65A inhibited Tm-cell activation,mimicking the neutralization by 5A12.This study provides not only a theoretical basis for a“CD147-Tm/Osteoclast-RA chain”for the potential prevention and treatment of RA or other T-cell-mediated autoimmune diseases but also a new target for related drug design and development.
基金supported by the National Science and Technology Major Project(2019ZX09732001,China)the National Basic Research Program of China(2015CB553701,China)
文摘Meplazumab is an anti-CD147 humanized IgG2 antibody.The purpose of this study was to characterize the nonclinical safety,tolerance and efficacy evaluation of meplazumab treating chloroquine resistant Plasmodium falciparum.Meplazumab was well tolerated in repeat-dose toxicology studies in cynomolgus monkeys.No observed adverse effect level was 12 mg/kg.No difference between genders in the primary toxicokinetic parameters after repeat intravenous injection of meplazumab.No increased levels of drug exposure and drug accumulation were observed in different gender and dose groups.Meplazumab had a low cross-reactivity rate in various tissues and did not cause hemolysis or aggregation of red blood cells.The biodistribution and excretion results indicated that meplazumab was mainly distributed in the plasma,whole blood,and hemocytes,and excreted in the urine.Moreover,meplazumab effectively inhibited the parasites from invading erythrocytes in humanized mice in a time-dependent manner and the efficacy is superior to that of chloroquine.All these studies suggested that meplazumab is safe and well tolerated in cynomolgus monkeys,and effectively inhibits P.falciparum from invading into human red blood cells.These nonclinical data facilitated the initiation of an ongoing clinical trial of meplazumab for antimalarial therapy.
文摘Cancer is a significant global health problem and remains one of the most challenging threats to human health. Conventional cancer treatments may include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Immunotherapy is still considered as a highly exciting field for new discoveries and treatments for cancer [1]. Immunotherapy was cited by Science as one of the top 10 breakthroughs in the world in 2013.
