Abstract
Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that enables T cells to express specific CARs on their surface, then returns these T cells to tumor patients to kill the corresponding tumor cells. Significant strides in CAR-T cell immunotherapy against hematologic malignancies have elicited research interest among scholars in the treatment of solid tumors. Nonetheless, in contrast with the efficacy of CAR-T cell immunotherapy in the treatment of hematologic malignancies, its general efficacy against solid tumors is insignificant. This has been attributed to the complex biological characteristics of solid tumors. CAR-T cells play a better role in solid tumors, for instance by addressing obstacles including the lack of specific targets, inhibition of tumor microenvironment (TME), homing barriers of CAR-T cells, differentiation and depletion of CAR-T cells, inhibition of immune checkpoints, trogocytosis of CAR-T cells, tumor antigen heterogeneity, etc. This paper reviews the obstacles influencing the efficacy of CAR-T cell immunotherapy in solid tumors, their mechanism, and coping strategies, as well as economic restriction of CAR-T cell immunotherapy and its solutions. It aims to provide some references for researchers to better overcome the obstacles that affect the efficacy of CAR-T cells in solid tumors.
Highlights
Malignant tumors present a serious global health issue with increasing annual incidence and high mortality rates
In contrast with hematologic malignancies, the activity maintenance time of CAR-T cells in patients with solid tumors was significantly shortened. These phenomena have been attributed to several reasons including (a) After injecting CAR-T cells into the body, they recognize, bind to, and kill the target cells, causing depletion of CAR-T cells; (b) Suppressive Tumor Microenvironment (TME); (c) Selecting specific subsets of T cells to construct CAR-T cells; (d) The design of CAR itself; (e) Whether CAR-T cells can be effectively activated in the body; (f) Differentiation type of CART cells
Researchers discovered that CAR-CD19-CD28-T cells and CAR-CD19-4-1BB-T cells exhibited different sensitivity to the density of tumor cell surface antigens. They combined these 2 types of CAR-T cells to counteract the effect of trogocytosis and significantly enhanced the therapeutic effect [60]. This mechanism of immune escape might be prevalent in CAR-T, trogocytosis of CAR-T cells can be counteracted via a combined use of different types of CAR-T cells
Summary
Malignant tumors present a serious global health issue with increasing annual incidence and high mortality rates. In contrast with hematologic malignancies, the activity maintenance time of CAR-T cells in patients with solid tumors was significantly shortened These phenomena have been attributed to several reasons including (a) After injecting CAR-T cells into the body, they recognize, bind to, and kill the target cells, causing depletion of CAR-T cells; (b) Suppressive TME; (c) Selecting specific subsets of T cells to construct CAR-T cells; (d) The design of CAR itself (for example, whether it contains costimulatory molecules and their number); (e) Whether CAR-T cells can be effectively activated in the body; (f) Differentiation type of CART cells. This mechanism of immune escape might be prevalent in CAR-T, trogocytosis of CAR-T cells can be counteracted via a combined use of different types of CAR-T cells
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