Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation throu...Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients.展开更多
For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for in...For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for inoperable sarcomas.In the 1970s,the Bacillus Calmette-Guérin(BCG)vaccine was repurposed,e.g.,for advanced melanomas.Then,therapeutic cancer vaccines based on tumorassociated antigens(found on the surfaces of cancer cells)were tried clinically but apparently have not made a really significant clinical impact.For repurposed pathogen vaccines,only the BCG vaccine was approved in 1989 for local application to treat nonmuscle-invading bladder cancers.Although the mildly toxic vaccine adjuvants deliberately added to conventional pathogen vaccines are appropriate for seasonal applications,when repurposed for continual oncology usage,toxicity may be problematic.In 2010,even with the approval of sipuleucel-T as the very first cancer vaccine(dendritic cell)developed for designated prostate cancers,it has also not made a really significant clinical impact.Perhaps more"user friendly"cancer vaccines should be explored.As from approximately 30 years ago,the safety and effectiveness of mRNA vaccination for oncology had already been studied,the current coronavirus disease 2019 pandemic,though disastrous,has given such progressively advancing technology a kickstart.For oncology,other virtues of mRNA vaccines seem advantageous,e.g.,rapid and versatile development,convenient modular design,and entirely cell-free synthesis,are being progressively recognized.Moreover,mRNAs encoding various oncology antigens for vaccination may also be tested with the combination of relatively non-toxic modalities of oncology treatments,e.g.,metformin or metronomic(low-dose,prolonged administration)chemotherapy.Admittedly,robust clinical data obtained through good quality clinical trials are mandatory.展开更多
Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances withi...Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.展开更多
Immunotherapy has rejuvenated cancer therapy,especially after anti-PD-(L)1 came onto the scene.Among the many therapeutic options,therapeutic cancer vaccines are one of the most essential players.Although great progre...Immunotherapy has rejuvenated cancer therapy,especially after anti-PD-(L)1 came onto the scene.Among the many therapeutic options,therapeutic cancer vaccines are one of the most essential players.Although great progress has been made in research on tumor antigen vaccines,few phase III trials have shown clinical benefits.One of the reasons lies in obstruction from the tumor microenvironment(TME).Meanwhile,the therapeutic cancer vaccine reshapes the TME in an ambivalent way,leading to immune stimulation or immune escape.In this review,we summarize recent progress on the interaction between therapeutic cancer vaccines and the TME.With respect to vaccine resistance,innate immunosuppressive TME components and acquired resistance caused by vaccination are both involved.Understanding the underlying mechanism of this crosstalk provides insight into the treatment of cancer by directly targeting the TME or synergizing with other therapeutics.展开更多
Herein,we firstly developed a non-covalent glycosylated gold nanoparticles/peptides nanovaccine which is assembled byβ-cyclodextrin(β-CD)based host-guest recognitions.This nanovaccine can generate significant titers...Herein,we firstly developed a non-covalent glycosylated gold nanoparticles/peptides nanovaccine which is assembled byβ-cyclodextrin(β-CD)based host-guest recognitions.This nanovaccine can generate significant titers of antibodies and improve the therapeutic effect against melanoma,suggesting the immunogenicity of peptide antigens can be improved by loading with this carrier.The novel vaccine carrier provides a platform for the transport of various antigens especially T cell-independent antigens.展开更多
Tumor vaccines,a type of personalized tumor immunotherapy,have developed rapidly in recent decades.These vaccines evoke tumor antigen-specific T cells to achieve immune recognition and killing of tumor cells.Because t...Tumor vaccines,a type of personalized tumor immunotherapy,have developed rapidly in recent decades.These vaccines evoke tumor antigen-specific T cells to achieve immune recognition and killing of tumor cells.Because the immunogenicity of tumor antigens alone is insufficient,immune adjuvants and nanocarriers are often required to enhance anti-tumor immune responses.At present,vaccine carrier development often integrates nanocarriers and immune adjuvants.Among them,outer membrane vesicles(OMVs)are receiving increasing attention as a delivery platform for tumor vaccines.OMVs are natural nanovesicles derived from Gramnegative bacteria,which have adjuvant function because they contain pathogen associated molecular patterns.Importantly,OMVs can be functionally modified by genetic engineering of bacteria,thus laying a foundation for applications as a delivery platform for tumor nanovaccines.This review summarizes 5 aspects of recent progress in,and future development of,OMV-based tumor nanovaccines:strain selection,heterogeneity,tumor antigen loading,immunogenicity and safety,and mass production of OMVs.展开更多
A facile and efficient strategy was established for the construction of RC-529 and its derivatives.Four conjugates of RC-529 derivatives with Tn antigen were synthesized and all elicited strong and T celldependent imm...A facile and efficient strategy was established for the construction of RC-529 and its derivatives.Four conjugates of RC-529 derivatives with Tn antigen were synthesized and all elicited strong and T celldependent immune responses in mice without requiring external adjuvants.In addition,all antisera induced by these conjugates could specifically recognize,bind to and kill Tn-overexpressing cancer cells.Thus,RC-529 shows promise as a useful platform for the development of new vaccine carriers with self-adjuvanting properties for the treatment of cancer.Moreover,preliminary structure-activity relationship analysis provides convincing support for further optimization of,and additional investigation into RC-529.展开更多
Patients exhibit good tolerance to messenger ribonucleic acid(m RNA)vaccines,and the choice of encoded molecules is flexible and diverse.These vaccines can be engineered to express full-length antigens containing mult...Patients exhibit good tolerance to messenger ribonucleic acid(m RNA)vaccines,and the choice of encoded molecules is flexible and diverse.These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex(MHC)restriction,are relatively easy to control and can be rapidly mass produced.In 2021,the U.S.Food and Drug Administration(FDA)approved the first m RNA-based coronavirus disease 2019(COVID-19)vaccine produced by Pfizer and Bio NTech,which has generated enthusiasm for m RNA vaccine research and development.Based on the above characteristics and the development of m RNA vaccines,m RNA cancer vaccines have become a research hotspot and have undergone rapid development,especially in the last five years.This review analyzes the advances in m RNA cancer vaccines from various perspectives,including the selection and expression of antigens/targets,the application of vectors and adjuvants,different administration routes,and preclinical evaluation,to reflect the trends and challenges associated with these vaccines.展开更多
Cervical cancer is a form of malignant tumor that seriously threatens women’s health. In China,according to the cancer statistics, 98,900 new cervical cancer cases and 30,500 deaths due to cervical cancer were estima...Cervical cancer is a form of malignant tumor that seriously threatens women’s health. In China,according to the cancer statistics, 98,900 new cervical cancer cases and 30,500 deaths due to cervical cancer were estimated to have occurred in2015, and the incidence and mortality rates still exhibited an upward trend[1].展开更多
Certain carbohydrate antigens of malignantly transformed cells have been identified as markers for the onset of cancer and have become targets for the development of anticancer vaccine therapies. For tumor antigens, m...Certain carbohydrate antigens of malignantly transformed cells have been identified as markers for the onset of cancer and have become targets for the development of anticancer vaccine therapies. For tumor antigens, many carbohydrate antigens belong to T-independent (TI) antigens. Carbohydrate conjugated to protein carriers can switch TI antigen to a T-dependent (TD) antigen. Attempts to add an innate immune response element (such as Toll-like receptor ligand) to carbohydrate TI-antigens have also been studied. Glycosylation inhibitors or small interfering RNA have also been used for antitumor and/or antiviral agents. This review aims at describing the vast spectrum of tumor carbohydrate antigens and strategies to develop cancer vaccines and drugs.展开更多
Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors wi...Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors with a suitable DNA can be a potential option for cancer treatment as a carrier for tumoricidal agents or bacterially directed Enzyme Prodrug treatment. Throughout this study, it is planned to have a review of the use of bacteria as vehicles by different ways for cancer treatment, detailing the systems of function and achievements at preclinical and clinical levels.展开更多
Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resist...Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.展开更多
With the establishment of the immune surveillance mechanism since the 1950s,attempts have been made to activate the immune system for cancer treatment through the discovery of various cytokines or the development of a...With the establishment of the immune surveillance mechanism since the 1950s,attempts have been made to activate the immune system for cancer treatment through the discovery of various cytokines or the development of antibodies up to now.The fruits of these efforts have contributed to the recognition of the 3rd generation of anticancer immunotherapy as the mainstream of cancer treatment.However,the limitations of cancer immunotherapy are also being recognized through the conceptual establishment of cold tumors recently,and colorectal cancer(CRC)has become a major issue from this therapeutic point of view.Here,it is emphasized that non-clinical strategies to overcome the immunosuppressive environment and clinical trials based on these basic investigations are being made on the journey to achieve better treatment outcomes for the treatment of cold CRC.展开更多
Gastric cancer(GC)is believed to be the fifth most common cancer and the third most common cause of death worldwide.Treatment techniques include radiation,chemotherapy,gastrectomy,and targeted treatments are often emp...Gastric cancer(GC)is believed to be the fifth most common cancer and the third most common cause of death worldwide.Treatment techniques include radiation,chemotherapy,gastrectomy,and targeted treatments are often employed.Some hopeful results from the development of GC immunotherapy have already changed treatment approaches.Along with previous combination medicines,new immunotherapies have been developed that target distinct molecules.Despite ongoing studies into the current therapeutic options and significant improvements in this field,the prognosis for the ailment is poor.Since there are few treatment options and a delay in detection,the illness actually advances,spreads,and metastasizes.The bulk of immunotherapies in use today rely on cytotoxic immune cells,monoclonal antibodies,and gene-transferred vaccines.Immune checkpoint inhibitors have become more popular.In this review,we sought to examine the viewpoint and development of several immunotherapy treatment modalities for advanced GC,as well as the clinical results thus far reported.Additionally,we outlined tumor immune escape and tumor immunosurveillance.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is an aggressive tumor with high lethality.Even with surgery,radiotherapy,chemotherapy,and other locoregional or systemic therapies,the survival rates for PDAC are low and have no...Pancreatic ductal adenocarcinoma(PDAC)is an aggressive tumor with high lethality.Even with surgery,radiotherapy,chemotherapy,and other locoregional or systemic therapies,the survival rates for PDAC are low and have not significantly changed in the past decades.The special characteristics of the PDAC’s microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this disease.PDAC is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T cells.The pancreatic microenvironment is a fibrotic,microvascularized stroma that isolates the tumor from systemic vascularization.Immunotherapy,a novel approach that has demonstrated effectiveness in certain solid tumors,has failed to show any practice-changing results in pancreatic cancer,with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden,which show prolonged survival rates with immunotherapy.Currently,numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell transfer,alone or in combination with other immunotherapeutic agents,chemoradiotherapy,and other targeted therapies.A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.展开更多
Therapeutic cancer vaccines have undergone a resurgence in the past decade.Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis,percutaneous vaccination is consid...Therapeutic cancer vaccines have undergone a resurgence in the past decade.Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis,percutaneous vaccination is considered to be an ideal treatment route.For convenient administration,the recent development of microneedles(MNs)provides a safe,painless,and low-cost transdermal delivery strategy,which could bypass the first-pass metabolism of vaccines for enhanced stability and bioavailability.However,the therapeutic effect of MNs-based cancer vaccines is not optimal,which is limited by the complex set of host,tumor,and environmental factors,as well as the limited vaccine loading capacity.Therefore,further improvements are still required to push their clinical translation.In this critical review,we deliberate on how to improve the therapeutic effect of MNs-based vaccines for cancer immunotherapy,summarize the recent advances in MNs-based cancer vaccination,and provide an overview of various design strategies and mechanisms for active or passive targeting delivery,aiming to develop safer,more effective,and more stable MNs-based cancer vaccines.Finally,we briefly describe the potential of vaccine platforms in combination with other therapies,suggest the need to design vaccines according to specific circumstances,and discuss the biosafety of repeated administration for enhancing clinical efficacy.展开更多
With the significant advances in cancer genomics using next-generation sequencing technologies,genomic and molecular profilingbased precision medicine is used as a part of routine clinical test for guiding and selecti...With the significant advances in cancer genomics using next-generation sequencing technologies,genomic and molecular profilingbased precision medicine is used as a part of routine clinical test for guiding and selecting the most appropriate treatments for individual cancer patients.Although many molecular-targeted therapies for a number of actionable genomic alterations have been developed,the clinical application of such information is still limited to a small proportion of cancer patients.In this review,we summarize the current status of personalized drug selection based on genomic and molecular profiling and highlight the challenges how we can further utilize the individual genomic information.Cancer immunotherapies,including immune checkpoint inhibitors,would be one of the potential approaches to apply the results of genomic sequencing most effectively.Highly cancer-specific antigens derived from somatic mutations,the so-called neoantigens,occurring in individual cancers have been in focus recently.Cancer immunotherapies,which target neoantigens,could lead to a precise treatment for cancer patients,despite the challenge in accurately predicting neoantigens that can induce cytotoxic T cells in individual patients.Precise prediction of neoantigens should accelerate the development of personalized immunotherapy including cancer vaccines and T-cell receptor-engineered T-cell therapy for a broader range of cancer patients.展开更多
Cancer immunotherapy harnesses the immune system to attack tumors and has received extensive attention in recent years.Cancer vaccines as an important branch of immunotherapy are designed for delivering tumor antigens...Cancer immunotherapy harnesses the immune system to attack tumors and has received extensive attention in recent years.Cancer vaccines as an important branch of immunotherapy are designed for delivering tumor antigens to antigen-presenting cells(APCs)to stimulate a strong immune response to against tumors,representing a potentially therapeutic and prophylactic effect with the long-term anticancer benefits.Nevertheless,the disappointing outcomes of their clinical use might be attributed to dilemma in antigen selection,immunogenicity,lymph nodes(LNs)targeting ability,lysosomal escape ability,immune evasion,etc.Nanotechnology,aiming to overcome these barriers,has been utilized in cancer vaccine development for decades.Numerous preclinical and clinical studies demonstrate positive results in nanomaterials-based cancer vaccines with considerable improvement in the vaccine efficacy.In this review,we systematically introduced the characteristics of nanovaccines and highlighted the different types of nanomaterials used for cancer vaccine design.In addition,the opportunities and challenges of the emerging nanotechnology-based cancer vaccines were discussed.展开更多
Hepatocellular carcinoma(HCC)is one of the world’s deadliest and fastestgrowing tumors,with a poor prognosis.HCC develops in the context of chronic liver disease.Curative resection,surgery(liver transplantation),tran...Hepatocellular carcinoma(HCC)is one of the world’s deadliest and fastestgrowing tumors,with a poor prognosis.HCC develops in the context of chronic liver disease.Curative resection,surgery(liver transplantation),trans-arterial chemoembolization,radioembolization,radiofrequency ablation and chemotherapy are common treatment options for HCC,however,they will only assist a limited percentage of patients.Current treatments for advanced HCC are ineffective and aggravate the underlying liver condition.Despite promising preclinical and early-phase clinical trials for some drugs,existing systemic therapeutic methods for advanced tumor stages remain limited,underlining an unmet clinical need.In current years,cancer immunotherapy has made significant progress,opening up new treatment options for HCC.HCC,on the other hand,has a variety of causes and can affects the body’s immune system via a variety of mechanisms.With the speedy advancement of synthetic biology and genetic engineering,a range of innovative immunotherapies,such as immune checkpoint inhibitors[anti-programmed cell death-1(PD-1),anti-cytotoxic T lymphocyte antigen-4,and anti-PD ligand 1 cell death antibodies],therapeutic cancer vaccines,engineered cytokines,and adoptive cell therapy have all been used for the treatment of advanced HCC.In this review,we summarize the present clinical and preclinical landscape of immunotherapies in HCC,critically discuss recent clinical trial outcomes,and address future perspectives in the field of liver cancer.展开更多
基金supported by a grant from the Strategic Priority Research Program of the Chinese Academy of Sciences(no.XDA09030303).
文摘Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients.
文摘For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for inoperable sarcomas.In the 1970s,the Bacillus Calmette-Guérin(BCG)vaccine was repurposed,e.g.,for advanced melanomas.Then,therapeutic cancer vaccines based on tumorassociated antigens(found on the surfaces of cancer cells)were tried clinically but apparently have not made a really significant clinical impact.For repurposed pathogen vaccines,only the BCG vaccine was approved in 1989 for local application to treat nonmuscle-invading bladder cancers.Although the mildly toxic vaccine adjuvants deliberately added to conventional pathogen vaccines are appropriate for seasonal applications,when repurposed for continual oncology usage,toxicity may be problematic.In 2010,even with the approval of sipuleucel-T as the very first cancer vaccine(dendritic cell)developed for designated prostate cancers,it has also not made a really significant clinical impact.Perhaps more"user friendly"cancer vaccines should be explored.As from approximately 30 years ago,the safety and effectiveness of mRNA vaccination for oncology had already been studied,the current coronavirus disease 2019 pandemic,though disastrous,has given such progressively advancing technology a kickstart.For oncology,other virtues of mRNA vaccines seem advantageous,e.g.,rapid and versatile development,convenient modular design,and entirely cell-free synthesis,are being progressively recognized.Moreover,mRNAs encoding various oncology antigens for vaccination may also be tested with the combination of relatively non-toxic modalities of oncology treatments,e.g.,metformin or metronomic(low-dose,prolonged administration)chemotherapy.Admittedly,robust clinical data obtained through good quality clinical trials are mandatory.
基金supported by grants from the National Clinical Research Center Cancer Fundthe Haihe Laboratory of Synthetic Biology(22HHSWSS00004)。
文摘Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.
基金the National Natural Science Foundation of China(81922048 and 81874112).
文摘Immunotherapy has rejuvenated cancer therapy,especially after anti-PD-(L)1 came onto the scene.Among the many therapeutic options,therapeutic cancer vaccines are one of the most essential players.Although great progress has been made in research on tumor antigen vaccines,few phase III trials have shown clinical benefits.One of the reasons lies in obstruction from the tumor microenvironment(TME).Meanwhile,the therapeutic cancer vaccine reshapes the TME in an ambivalent way,leading to immune stimulation or immune escape.In this review,we summarize recent progress on the interaction between therapeutic cancer vaccines and the TME.With respect to vaccine resistance,innate immunosuppressive TME components and acquired resistance caused by vaccination are both involved.Understanding the underlying mechanism of this crosstalk provides insight into the treatment of cancer by directly targeting the TME or synergizing with other therapeutics.
基金the Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine(No.20188030322011)the National Natural Science Foundation of China(No.81773580)。
文摘Herein,we firstly developed a non-covalent glycosylated gold nanoparticles/peptides nanovaccine which is assembled byβ-cyclodextrin(β-CD)based host-guest recognitions.This nanovaccine can generate significant titers of antibodies and improve the therapeutic effect against melanoma,suggesting the immunogenicity of peptide antigens can be improved by loading with this carrier.The novel vaccine carrier provides a platform for the transport of various antigens especially T cell-independent antigens.
基金supported by grants from the National Key R&D Program of China(Grant No.2021YFA0909900,X.Z.)the CAS Project for Young Scientists in Basic Research(Grant No.YSBR-010,X.Z.)+2 种基金the Beijing Natural Science Foundation(Grant No.Z200020,X.Z.)the Beijing Nova Program(Grant No.Z201100006820031,X.Z.)the National Natural Science Foundation of China(Grant No.32171384,X.Z.).
文摘Tumor vaccines,a type of personalized tumor immunotherapy,have developed rapidly in recent decades.These vaccines evoke tumor antigen-specific T cells to achieve immune recognition and killing of tumor cells.Because the immunogenicity of tumor antigens alone is insufficient,immune adjuvants and nanocarriers are often required to enhance anti-tumor immune responses.At present,vaccine carrier development often integrates nanocarriers and immune adjuvants.Among them,outer membrane vesicles(OMVs)are receiving increasing attention as a delivery platform for tumor vaccines.OMVs are natural nanovesicles derived from Gramnegative bacteria,which have adjuvant function because they contain pathogen associated molecular patterns.Importantly,OMVs can be functionally modified by genetic engineering of bacteria,thus laying a foundation for applications as a delivery platform for tumor nanovaccines.This review summarizes 5 aspects of recent progress in,and future development of,OMV-based tumor nanovaccines:strain selection,heterogeneity,tumor antigen loading,immunogenicity and safety,and mass production of OMVs.
基金supported by the National Natural Science Foundation of China(Nos.81773580,82003594)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme to Guochao Liao(2019)+1 种基金the Department of education of Guangdong Province,China(No.2020KZDZX1057)the Science and Technology Planning Program of Guangzhou City,China(No.202008040004)。
文摘A facile and efficient strategy was established for the construction of RC-529 and its derivatives.Four conjugates of RC-529 derivatives with Tn antigen were synthesized and all elicited strong and T celldependent immune responses in mice without requiring external adjuvants.In addition,all antisera induced by these conjugates could specifically recognize,bind to and kill Tn-overexpressing cancer cells.Thus,RC-529 shows promise as a useful platform for the development of new vaccine carriers with self-adjuvanting properties for the treatment of cancer.Moreover,preliminary structure-activity relationship analysis provides convincing support for further optimization of,and additional investigation into RC-529.
文摘Patients exhibit good tolerance to messenger ribonucleic acid(m RNA)vaccines,and the choice of encoded molecules is flexible and diverse.These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex(MHC)restriction,are relatively easy to control and can be rapidly mass produced.In 2021,the U.S.Food and Drug Administration(FDA)approved the first m RNA-based coronavirus disease 2019(COVID-19)vaccine produced by Pfizer and Bio NTech,which has generated enthusiasm for m RNA vaccine research and development.Based on the above characteristics and the development of m RNA vaccines,m RNA cancer vaccines have become a research hotspot and have undergone rapid development,especially in the last five years.This review analyzes the advances in m RNA cancer vaccines from various perspectives,including the selection and expression of antigens/targets,the application of vectors and adjuvants,different administration routes,and preclinical evaluation,to reflect the trends and challenges associated with these vaccines.
基金supported by the Natural Science Foundation of Hubei Province,China [Grant No.2017CKC891]the Health Commission Of Hubei Province,China [Grant No.WJ2019H286]
文摘Cervical cancer is a form of malignant tumor that seriously threatens women’s health. In China,according to the cancer statistics, 98,900 new cervical cancer cases and 30,500 deaths due to cervical cancer were estimated to have occurred in2015, and the incidence and mortality rates still exhibited an upward trend[1].
基金Supported by the National Outstanding Youth Foundation of China (81025008)the National Natural Science Foundation of China (30921001,30800038, 31270176 and 81000714)+1 种基金the National Grand Program on Important Infectious Disease (2012ZX10003002-015)the National Basic Research Program of China (973 Program, 2009CB522507 and 2012CB720604)
文摘Certain carbohydrate antigens of malignantly transformed cells have been identified as markers for the onset of cancer and have become targets for the development of anticancer vaccine therapies. For tumor antigens, many carbohydrate antigens belong to T-independent (TI) antigens. Carbohydrate conjugated to protein carriers can switch TI antigen to a T-dependent (TD) antigen. Attempts to add an innate immune response element (such as Toll-like receptor ligand) to carbohydrate TI-antigens have also been studied. Glycosylation inhibitors or small interfering RNA have also been used for antitumor and/or antiviral agents. This review aims at describing the vast spectrum of tumor carbohydrate antigens and strategies to develop cancer vaccines and drugs.
文摘Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors with a suitable DNA can be a potential option for cancer treatment as a carrier for tumoricidal agents or bacterially directed Enzyme Prodrug treatment. Throughout this study, it is planned to have a review of the use of bacteria as vehicles by different ways for cancer treatment, detailing the systems of function and achievements at preclinical and clinical levels.
基金supported by the National Natural Science Foundation of China (31970696, 81502975, 82188102, and 81830089)Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar (LR22H160010)+2 种基金National Key Research and Development Program of China (2019YFC1316000)Zhejiang Provincial Key Research and Development Program (2019C03019)Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program (Young Talent Program)(2022R40122)
文摘Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.
文摘With the establishment of the immune surveillance mechanism since the 1950s,attempts have been made to activate the immune system for cancer treatment through the discovery of various cytokines or the development of antibodies up to now.The fruits of these efforts have contributed to the recognition of the 3rd generation of anticancer immunotherapy as the mainstream of cancer treatment.However,the limitations of cancer immunotherapy are also being recognized through the conceptual establishment of cold tumors recently,and colorectal cancer(CRC)has become a major issue from this therapeutic point of view.Here,it is emphasized that non-clinical strategies to overcome the immunosuppressive environment and clinical trials based on these basic investigations are being made on the journey to achieve better treatment outcomes for the treatment of cold CRC.
文摘Gastric cancer(GC)is believed to be the fifth most common cancer and the third most common cause of death worldwide.Treatment techniques include radiation,chemotherapy,gastrectomy,and targeted treatments are often employed.Some hopeful results from the development of GC immunotherapy have already changed treatment approaches.Along with previous combination medicines,new immunotherapies have been developed that target distinct molecules.Despite ongoing studies into the current therapeutic options and significant improvements in this field,the prognosis for the ailment is poor.Since there are few treatment options and a delay in detection,the illness actually advances,spreads,and metastasizes.The bulk of immunotherapies in use today rely on cytotoxic immune cells,monoclonal antibodies,and gene-transferred vaccines.Immune checkpoint inhibitors have become more popular.In this review,we sought to examine the viewpoint and development of several immunotherapy treatment modalities for advanced GC,as well as the clinical results thus far reported.Additionally,we outlined tumor immune escape and tumor immunosurveillance.
基金by the Instituto de Salud Carlos III,Ministerio de Economia,Industria y Competitividad,No.PI18/01604.
文摘Pancreatic ductal adenocarcinoma(PDAC)is an aggressive tumor with high lethality.Even with surgery,radiotherapy,chemotherapy,and other locoregional or systemic therapies,the survival rates for PDAC are low and have not significantly changed in the past decades.The special characteristics of the PDAC’s microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this disease.PDAC is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T cells.The pancreatic microenvironment is a fibrotic,microvascularized stroma that isolates the tumor from systemic vascularization.Immunotherapy,a novel approach that has demonstrated effectiveness in certain solid tumors,has failed to show any practice-changing results in pancreatic cancer,with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden,which show prolonged survival rates with immunotherapy.Currently,numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell transfer,alone or in combination with other immunotherapeutic agents,chemoradiotherapy,and other targeted therapies.A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.
基金supported by the National Natural Science Foundation of China(No.82073799)the Natural Science Foundation of Hunan Province in China(No.2021JJ20084)the Science and Technology Innovation Program of Hunan Province(No.2021RC3020)。
文摘Therapeutic cancer vaccines have undergone a resurgence in the past decade.Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis,percutaneous vaccination is considered to be an ideal treatment route.For convenient administration,the recent development of microneedles(MNs)provides a safe,painless,and low-cost transdermal delivery strategy,which could bypass the first-pass metabolism of vaccines for enhanced stability and bioavailability.However,the therapeutic effect of MNs-based cancer vaccines is not optimal,which is limited by the complex set of host,tumor,and environmental factors,as well as the limited vaccine loading capacity.Therefore,further improvements are still required to push their clinical translation.In this critical review,we deliberate on how to improve the therapeutic effect of MNs-based vaccines for cancer immunotherapy,summarize the recent advances in MNs-based cancer vaccination,and provide an overview of various design strategies and mechanisms for active or passive targeting delivery,aiming to develop safer,more effective,and more stable MNs-based cancer vaccines.Finally,we briefly describe the potential of vaccine platforms in combination with other therapies,suggest the need to design vaccines according to specific circumstances,and discuss the biosafety of repeated administration for enhancing clinical efficacy.
基金This work was partly supported by Japan Agency for Medical Research and Development(Grant Nos.17ck0106364h0003 and 20ck0106543h0001)the Japan Society for the Promotion of Science(Grant No.19H03522).
文摘With the significant advances in cancer genomics using next-generation sequencing technologies,genomic and molecular profilingbased precision medicine is used as a part of routine clinical test for guiding and selecting the most appropriate treatments for individual cancer patients.Although many molecular-targeted therapies for a number of actionable genomic alterations have been developed,the clinical application of such information is still limited to a small proportion of cancer patients.In this review,we summarize the current status of personalized drug selection based on genomic and molecular profiling and highlight the challenges how we can further utilize the individual genomic information.Cancer immunotherapies,including immune checkpoint inhibitors,would be one of the potential approaches to apply the results of genomic sequencing most effectively.Highly cancer-specific antigens derived from somatic mutations,the so-called neoantigens,occurring in individual cancers have been in focus recently.Cancer immunotherapies,which target neoantigens,could lead to a precise treatment for cancer patients,despite the challenge in accurately predicting neoantigens that can induce cytotoxic T cells in individual patients.Precise prediction of neoantigens should accelerate the development of personalized immunotherapy including cancer vaccines and T-cell receptor-engineered T-cell therapy for a broader range of cancer patients.
基金supported by the National Science Foundation for Excellent Young Scholars(No.32122052)National Natural Science Foundation Regional Innovation and Development(No.U19A2003).
文摘Cancer immunotherapy harnesses the immune system to attack tumors and has received extensive attention in recent years.Cancer vaccines as an important branch of immunotherapy are designed for delivering tumor antigens to antigen-presenting cells(APCs)to stimulate a strong immune response to against tumors,representing a potentially therapeutic and prophylactic effect with the long-term anticancer benefits.Nevertheless,the disappointing outcomes of their clinical use might be attributed to dilemma in antigen selection,immunogenicity,lymph nodes(LNs)targeting ability,lysosomal escape ability,immune evasion,etc.Nanotechnology,aiming to overcome these barriers,has been utilized in cancer vaccine development for decades.Numerous preclinical and clinical studies demonstrate positive results in nanomaterials-based cancer vaccines with considerable improvement in the vaccine efficacy.In this review,we systematically introduced the characteristics of nanovaccines and highlighted the different types of nanomaterials used for cancer vaccine design.In addition,the opportunities and challenges of the emerging nanotechnology-based cancer vaccines were discussed.
文摘Hepatocellular carcinoma(HCC)is one of the world’s deadliest and fastestgrowing tumors,with a poor prognosis.HCC develops in the context of chronic liver disease.Curative resection,surgery(liver transplantation),trans-arterial chemoembolization,radioembolization,radiofrequency ablation and chemotherapy are common treatment options for HCC,however,they will only assist a limited percentage of patients.Current treatments for advanced HCC are ineffective and aggravate the underlying liver condition.Despite promising preclinical and early-phase clinical trials for some drugs,existing systemic therapeutic methods for advanced tumor stages remain limited,underlining an unmet clinical need.In current years,cancer immunotherapy has made significant progress,opening up new treatment options for HCC.HCC,on the other hand,has a variety of causes and can affects the body’s immune system via a variety of mechanisms.With the speedy advancement of synthetic biology and genetic engineering,a range of innovative immunotherapies,such as immune checkpoint inhibitors[anti-programmed cell death-1(PD-1),anti-cytotoxic T lymphocyte antigen-4,and anti-PD ligand 1 cell death antibodies],therapeutic cancer vaccines,engineered cytokines,and adoptive cell therapy have all been used for the treatment of advanced HCC.In this review,we summarize the present clinical and preclinical landscape of immunotherapies in HCC,critically discuss recent clinical trial outcomes,and address future perspectives in the field of liver cancer.
