In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved u...In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved understanding of theoretical basis, such as molecular biology and immunology. Thereinto, adoptive cellular immunotherapy （ACI） has become one of the hotspots, which comprises a variety of treatment approaches, such as TIL, CIK cell, ~＇~ T cell, CAR-engineered T cell and Allogeneie stem cell transplantation （alloSCT）. Although preclinical efficacy has been demonstrated remarkably, clinical trials could not consistently show the benefit due to multi-factors in complex immnnosuppressive microenvironment in vivo compared to that of in vitro. Here we review some timely aspects of ACI for advanced urologic malignancies, and describe the current status and limitation of immunotherapy from the cellular level. It＇s our expectation to provide prompting consideration of novel combinatorial ACI strategies and a resurgence of interest in ACI for advanced urologic malignancies.展开更多
Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions.Conventional systemic chemotherapy has failed in HCC,and th...Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions.Conventional systemic chemotherapy has failed in HCC,and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory.Data sources:Literature search was conducted in Pub Med for relevant articles published before January 2021.The search aimed to identify recent developments in immune-based treatment approaches for HCC.Information of clinical trials was obtained from https://clinicaltrials.gov/.Results:Two immune checkpoint inhibitors(ICIs),nivolumab and pembrolizumab were approved as monotherapies,which has revolutionized HCC treatment.Besides,combination ICIs have also got accelerated FDA approval recently.Immune-based therapies have challenged targeted drugs owing to their safety,tolerability,and survival benefits.In addition to the significant success in ICIs,other immunotherapeutic strategies such as cancer vaccine,chimeric antigen receptor T-cells,natural killer cells,cytokines,and combination therapy,have also shown promising outcomes in clinical trials.Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs.Conclusions:Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years.However,challenges such as low response rate and acquired resistance in previously respondent patients still exist.Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.展开更多
Hepatocellular carcinoma(HCC)is one of the deadliest and most common malignancies of the liver.Considering the rich immune background of carcinogenesis in HCC,efforts have been focused on further understanding the rol...Hepatocellular carcinoma(HCC)is one of the deadliest and most common malignancies of the liver.Considering the rich immune background of carcinogenesis in HCC,efforts have been focused on further understanding the role of the immune system in tumor suppression and promotion.The utilization of immunotherapy in HCC has led to encouraging results that has translated to longer survival and better quality of life among patients.The development of novel HCC-tailored regimens such as vaccine therapy and adoptive cellular therapy coupled with a deeper understanding of biomarkers predictive of the response to immunotherapy will lead to better treatment outcomes.展开更多
Adoptive immunotherapy,notably involving chimeric antigen receptor(CAR)-T cells,has obtained Food and Drug Administration(FDA)approval as a treatment for various hematological malignancies,demonstrating promising prec...Adoptive immunotherapy,notably involving chimeric antigen receptor(CAR)-T cells,has obtained Food and Drug Administration(FDA)approval as a treatment for various hematological malignancies,demonstrating promising preclinical efficacy against cancers.However,the intricate and resource-intensive autologous cell processing,encompassing collection,expansion,engineering,isolation,and administration,hamper the efficacy of this therapeutic modality.Furthermore,conventional CAR T therapy is presently confined to addressing solid tumors due to impediments posed by physical barriers,the potential for cytokine release syndrome,and cellular exhaustion induced by the immunosuppressive and heterogeneous tumor microenvironment.Consequently,a strategic integration of adoptive immunotherapy with synergistic multimodal treatments,such as chemotherapy,radiotherapy,and vaccine therapy etc.,emerges as a pivotal approach to surmount these inherent challenges.This collaborative strategy holds the key to addressing the limitations delineated above,thereby facilitating the realization of more precise personalized therapies characterized by heightened therapeutic efficacy.Such synergistic strategy not only serves to mitigate the constraints associated with adoptive immunotherapy but also fosters enhanced clinical applicability,thereby advancing the frontiers of therapeutic precision and effectiveness.展开更多
基金supported by a grant from National Natural Science Foundation of China(No.30901481,81372752,81472411)Wu-Jie Ping Medical Foundation(320.6750.13261)
文摘In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved understanding of theoretical basis, such as molecular biology and immunology. Thereinto, adoptive cellular immunotherapy （ACI） has become one of the hotspots, which comprises a variety of treatment approaches, such as TIL, CIK cell, ~＇~ T cell, CAR-engineered T cell and Allogeneie stem cell transplantation （alloSCT）. Although preclinical efficacy has been demonstrated remarkably, clinical trials could not consistently show the benefit due to multi-factors in complex immnnosuppressive microenvironment in vivo compared to that of in vitro. Here we review some timely aspects of ACI for advanced urologic malignancies, and describe the current status and limitation of immunotherapy from the cellular level. It＇s our expectation to provide prompting consideration of novel combinatorial ACI strategies and a resurgence of interest in ACI for advanced urologic malignancies.
基金supported by grants from the National S&T Major Project(2017ZX10203205)Key Research&Development Plan of Zhejiang Province(2019C03050)。
文摘Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions.Conventional systemic chemotherapy has failed in HCC,and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory.Data sources:Literature search was conducted in Pub Med for relevant articles published before January 2021.The search aimed to identify recent developments in immune-based treatment approaches for HCC.Information of clinical trials was obtained from https://clinicaltrials.gov/.Results:Two immune checkpoint inhibitors(ICIs),nivolumab and pembrolizumab were approved as monotherapies,which has revolutionized HCC treatment.Besides,combination ICIs have also got accelerated FDA approval recently.Immune-based therapies have challenged targeted drugs owing to their safety,tolerability,and survival benefits.In addition to the significant success in ICIs,other immunotherapeutic strategies such as cancer vaccine,chimeric antigen receptor T-cells,natural killer cells,cytokines,and combination therapy,have also shown promising outcomes in clinical trials.Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs.Conclusions:Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years.However,challenges such as low response rate and acquired resistance in previously respondent patients still exist.Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.
文摘Hepatocellular carcinoma(HCC)is one of the deadliest and most common malignancies of the liver.Considering the rich immune background of carcinogenesis in HCC,efforts have been focused on further understanding the role of the immune system in tumor suppression and promotion.The utilization of immunotherapy in HCC has led to encouraging results that has translated to longer survival and better quality of life among patients.The development of novel HCC-tailored regimens such as vaccine therapy and adoptive cellular therapy coupled with a deeper understanding of biomarkers predictive of the response to immunotherapy will lead to better treatment outcomes.
基金supported by start-up package funding from The Hong Kong Polytechnic University(Y.C.).
文摘Adoptive immunotherapy,notably involving chimeric antigen receptor(CAR)-T cells,has obtained Food and Drug Administration(FDA)approval as a treatment for various hematological malignancies,demonstrating promising preclinical efficacy against cancers.However,the intricate and resource-intensive autologous cell processing,encompassing collection,expansion,engineering,isolation,and administration,hamper the efficacy of this therapeutic modality.Furthermore,conventional CAR T therapy is presently confined to addressing solid tumors due to impediments posed by physical barriers,the potential for cytokine release syndrome,and cellular exhaustion induced by the immunosuppressive and heterogeneous tumor microenvironment.Consequently,a strategic integration of adoptive immunotherapy with synergistic multimodal treatments,such as chemotherapy,radiotherapy,and vaccine therapy etc.,emerges as a pivotal approach to surmount these inherent challenges.This collaborative strategy holds the key to addressing the limitations delineated above,thereby facilitating the realization of more precise personalized therapies characterized by heightened therapeutic efficacy.Such synergistic strategy not only serves to mitigate the constraints associated with adoptive immunotherapy but also fosters enhanced clinical applicability,thereby advancing the frontiers of therapeutic precision and effectiveness.
文摘目的:观察自体DC-CIK细胞联合经皮微波热凝(percutaneous microwave coagulation therapy,PMCT)治疗肝癌的临床疗效。方法:收集2012年1月至2014年2月东方肝胆外科医院生物治疗科收治的44例行PMCT+DC-CIK治疗的肝癌患者(联合治疗组),先行血细胞分离单采并进行DC-CIK细胞培养,采血后第2天进行PMCT治疗;培养10 d后行CIK细胞回输及DC疫苗皮内注射。此后分别于1、2个月后行第2疗程及第3疗程DC-CIK细胞治疗。同时选取44例单纯行PMCT治疗的同期肝癌患者与之配对(对照组),该组患者仅行PMCT治疗。观察两组治疗前后的AFP变化、免疫功能、无进展生存期、总生存期及不良反应。结果:联合治疗组、对照组治疗后均有AFP下降及外周血调节性T细胞降低,但联合治疗组下降程度更显著(P<0.05);对照组治疗后外周血淋巴细胞亚群无明显变化(P>0.05),而联合治疗组则显著升高(P<0.05)。联合治疗组中位无进展生存时间及中位总生存时间均较对照组延长(7.1 vs 4.9个月;21.5 vs 14.0个月,均P<0.05)。结论:自体DC-CIK细胞联合PMCT是治疗肝癌的一种有效方法,可提高患者免疫功能、延缓肿瘤复发、延长生存期,且不良反应较少。
