Novel strategies to overcome obstacles in the solid tumour microenvironment for CAR-T cell therapy

By harnessing the power of the patient’s immune system to recognize and eliminate cancer cells, chimeric antigen receptor T (CAR-T) cells represent a paradigm shift in cancer treatment. The FDA approval of CAR-T represents a significant milestone in the field of cancer therapy, as it provides a promising treatment option for patients with refractory or relapsed cancer who have exhausted all conventional treatment modalities. However, the internal obstacles of the tumour microenvironment (TME) have hindered its success, especially for solid tumours, as it poses several barriers to preventing the activity of CAR-T therapy. The aspects of the TME that have hampered CAR-T cell efficacy along with suggestions for the future will be reviewed in this paper. Several research has been conducted to investigate possible novel approaches to overcome the obstacles presented when dealing with solid tumours. Recent advances in the field of CAR-T therapy have led to development of innovative strategies to improve the capacity of CAR-T cells to infiltrate solid tumours. These approaches involve either local administration or targeting angiogenesis to overcome physical barriers. Novel engineering methods of CAR-T cells have also been highlighted by targeting immunosuppressive factors. In addition, approaches focusing on simultaneous stimulation of bystander endogenous antitumour responses have also been investigated. In-depth studies of the application of CAR-T therapy in solid tumour and tackling the existing obstacles are of great value for the long-term strategy of treating cancer patients in a more efficient way.