Adoptive cell therapy for solid tumors: Chimeric antigen receptor T cells and beyond

Adoptive cell therapy with chimeric antigen receptor T cells has caused a significant revolution in the treatment of hematological malignancies. Unfortunately, for solid tumors, this treatment modality has been proven insufficient to achieve significant antitumor activity. The use of modified T cell receptors towards tumor-associated antigens (NY-ESO, MAGE-A4) has recently shown antitumor activity in synovial sarcoma. Also, treatment with tumor-infiltrating lymphocytes shows clinical activity in metastatic cervical cancer and melanoma resistant to checkpoint inhibitors. Strategies to improve results and broaden the applicability of therapeutic lymphocytes for solid tumors include local delivery, fourth generation chimeric antigen receptor T cells, off-the-shelf T lymphocytes and private neoantigen-directed cells, among others. In this review, we summarize the status of adoptive cell therapy using T cells for solid tumors and the investigational strategies being tested in this field.