CAR-T Cells: Overcoming Barriers and Breaking Boundaries in Cancer Immunotherapy

Chimeric antigen receptor (CAR) immunotherapy has made significant strides, particularly in hematological malignancies, with five CAR T therapies gaining FDA approval. However, its application in solid tumors remains challenging due to issues like poor CAR T cell trafficking, an immunosuppressive tumor microenvironment (TME), and therapy-related toxicity. CAR Natural Killer (NK) cells present an alternative with advantages such as multiple mechanisms for targeting cancer and reduced side effects. Additionally, macrophages, which naturally infiltrate tumors, are under investigation for CAR therapy to overcome the limitations seen in CAR T and CAR NK approaches. In this review, our primary focus will be on solid tumors, as they present unique challenges in CAR T cell therapy, such as poor trafficking and the immunosuppressive tumor microenvironment. However, we will also address some hematological malignancies, particularly those with poor prognoses, where similar issues of CAR T cell dysfunction and lack of persistence are observed. By covering both solid tumors and certain blood cancers, we aim to provide a comprehensive understanding of the barriers and potential strategies for improving CAR T cell therapies across different malignancies.