Challenges and strategies of chimeric antigen receptor T-cell therapy in solid tumors
Li Xingning, Qu Chunfeng
Department of Immunology National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital Chinese Academy
of Medical Sciences and Peking Union Medical College Beijing 100021 China
Abstract：Adoptive cell therapy is the process of regulating patients ' own immune system through the administration of
tumor-reactive immune cells to achieve the goal of eliminating tumor cells. CAR-T cell is genetically modified T cell and the CAR-T
cell therapy is a kind of adoptive T-cell therapy. Compared with generally adoptive cell therapy for tumors CAR-T cell therapy offers
the advantages of higher specificity and stronger cytotoxicity on tumor cells and prolonged curative efficacy. In the treatment of
hematological malignancies CAR - T cell therapy proves effective. An increasing number of preclinical studies and corresponding
clinical studies have been carried out to extend CAR - T cell therapy to the treatment of some solid tumors such as metastatic
melanoma non-small cell lung cancer breast cancer and colorectal cancer. However it has not achieved good curative efficacy.
Owing to the differences in properties between solid solid tumors and hematological malignancies CAR-T cell therapy is challenged for
the treatment of the solid tumors such as on - target off - tumor toxicity immune escape caused by tumor antigen heterogeneity
CAR- T cell exhaustion due to the immunosuppressive tumor microenvironment resulting in the limited therapeutic efficacy and
immune toxicity. To improve the clinical efficacy and safety of CAR-T cell therapy in the treatment of the solid tumors many different
strategies are developing currently based on the unique characteristics of solid tumors such as overexpressing chemokine receptors and
cytokines dual CAR-T cells improving T cell metabolism adjusting the affinity of CAR. To provide a reference for future CAR-T
cell therapy for solid tumors the development of CAR-T cells current challenges and associated optimization strategies for CAR-T
cells in solid tumor treatment are reviewed in this paper.
