T-cell receptor （TCR）-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR- engineered T cells began more than two decades ago, w...T-cell receptor （TCR）-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR- engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR- engineered T cells to target New York esophageal squamous cell carcinoma （NY-ESO-1）. These successes demonstrate the potential of this approach to treat cancer. In this review, we provide a perspective on the current and future applications of TCR-engineered T cells for the treatment of cancer. Our summary focuses on TCR activation and both pre-clinical and clinical applications of TCR-engineered T cells. We also discuss how to enhance the function of TCR-engineered T cells and prolong their longevity in the tumor microenvironment.展开更多
Chimeric antigen receptor T(CAR-T)cell therapy achieved advanced progress in the treatment of hematological tumors.However,the application of CAR-T cell therapy for solid tumors still faces many challenges.Competition...Chimeric antigen receptor T(CAR-T)cell therapy achieved advanced progress in the treatment of hematological tumors.However,the application of CAR-T cell therapy for solid tumors still faces many challenges.Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy’s low effectiveness.Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment,which is characterized by increased interstitial fluid pressure,low pH level,hypoxia,accumulation of immunosuppressive metabolites,and mitochondrial dysfunction.These factors are important contributors to restriction of T cell proliferation,cytokine release,and suppression of tumor cell-killing ability.This review provides an overview of how different metabolites regulate T cell activity,analyzes the current dilemmas,and proposes key strategies to reestablish the CAR-T cell therapy’s effectiveness through targeting metabolism,with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.展开更多
文摘T-cell receptor （TCR）-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR- engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR- engineered T cells to target New York esophageal squamous cell carcinoma （NY-ESO-1）. These successes demonstrate the potential of this approach to treat cancer. In this review, we provide a perspective on the current and future applications of TCR-engineered T cells for the treatment of cancer. Our summary focuses on TCR activation and both pre-clinical and clinical applications of TCR-engineered T cells. We also discuss how to enhance the function of TCR-engineered T cells and prolong their longevity in the tumor microenvironment.
基金National Key Research and Development Program Intergovernmental Key Project for International Science and Technology Innovation Cooperation(No.2022YFE0141000)Natural Science Foundation of China(No.82203548)+2 种基金China Postdoctoral Science Foundation Project(No.2022M712894)Medical Science and Technology Project of Henan Province(No.LHGJ20220385)Major science and technology project of Henan Province(No.221100310100)
文摘Chimeric antigen receptor T(CAR-T)cell therapy achieved advanced progress in the treatment of hematological tumors.However,the application of CAR-T cell therapy for solid tumors still faces many challenges.Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy’s low effectiveness.Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment,which is characterized by increased interstitial fluid pressure,low pH level,hypoxia,accumulation of immunosuppressive metabolites,and mitochondrial dysfunction.These factors are important contributors to restriction of T cell proliferation,cytokine release,and suppression of tumor cell-killing ability.This review provides an overview of how different metabolites regulate T cell activity,analyzes the current dilemmas,and proposes key strategies to reestablish the CAR-T cell therapy’s effectiveness through targeting metabolism,with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.
