Cellular therapies for solid cancer: clinical experience, challenges and future revolution

Adoptive cell therapy (ACT) is a form of immunotherapy in which cancer-specific T cells are modified and expanded ex vivo and re-infused to target and eradicate the tumor. Chimeric antigen receptor (CAR) engineered T cell therapy has shown transformational clinical benefit in hematologic malignancies, but its application to solid tumors has been challenging. This review follows the evolution of ACT from initial insights to the implementation of treatment protocols, focusing on the predicaments during early trials for solid cancers with this treatment. While there is evidence for effective and durable immune rejection of refractory solid malignancies with adoptive cell transfer, the clinical experience disclosed key limitations and provided the impetus for developing the next iterations of cellular therapy products. Future directions of ACT are discussed, in particular with regard to genetic engineering of autologous cells, selection of appropriate targets and optimizing treatment regimens in the era of checkpoint inhibitors.

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