Tumor-Infiltrating Lymphocytes, CAR-, and T-Cell Receptor-Modified T Cells in Solid Cancer Oncology

Background: Adoptive cellular therapy (ACT) is a promising treatment approach aiming at enhancing T-cell antitumor immune response. ACT includes tumor-infiltrating lymphocytes, chimeric antigen receptor (CAR) and T-cell receptor gene-modified T cells. Despite a milestone achievement with CAR-T cells in hematopoietic malignancies, ACT has shown modest clinical responses in refractory solid cancers and durable responses remain limited to a minor fraction of patients. Summary: In this review, we highlight major advances, limitations and current developments of T-cell therapies for solid cancers. We discuss emerging promising strategies as next-generation ACT, exploring local delivery routes to maximize efficacy and improve safety, integrating predictive biomarkers to optimize selection of patients who most likely would benefit from ACT, using combination therapy to overcome the immunosuppressive tumor microenvironment, targeting multiple tumor antigen to avoid tumor antigen escape, selection of the most potent T-cell product to overcome T-cell dysfunction, and incorporating cutting-edge new technologies, such as gene-editing to further improve antitumor T-cell functions and reduce therapy-related toxicity. Key Messages: Advances made in ACT trials have move the field of immunotherapy for refractory solid cancers to a new stage, by constantly incorporating new strategies to develop next-generation therapies designed to enhance efficacy and improve safety and to allow a broaden access to a large numbers of patients.