CAR designs for solid tumors: overcoming hurdles and paving the way for effective immunotherapy

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized immunotherapy by modifying patients' immune cells genetically. By expressing CARs, these modified cells can specifically identify and eliminate tumor cells. The success of CAR-T therapy in hematological malignancies, such as leukemia and lymphoma, has been remarkable. Numerous studies have reported improved patient outcomes and increased survival rates. However, the application of CAR-T therapy in treating solid tumors faces significant challenges. Solid tumors possess complex microenvironments containing stromal cells, extracellular matrix components, and blood vessels. These factors can impede the infiltration and persistence of CAR-T cells within the tumor. Additionally, the lack of target antigens exclusively expressed on tumor cells raises concerns about off-target effects and potential toxicity. This review aims to discuss advancements achieved by CAR-T therapy in solid tumors and the clinical outcomes in the realm of solid tumors.

Graphical abstract

Keywords

Chimeric antigen receptor T cell / Solid tumor / Immunotherapy

Acknowledgements

This review was supported by National Natural Science Foundation of China (81972672); The University Grants Committee/Research Grants Council of the Hong Kong Special Administrative Region, China (AoE/M-401/20), Innovation and Technology Fund (ITF). Guangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Diseases (2019B121205010); Basic Research Project of Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (GIBHBRP23-03). International Partnership Program of the Chinese Academy of Sciences (188GJHZ2022015GC).

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