Adoptive Cell Therapy—Tumor-Infiltrating Lymphocytes, T-Cell Receptors, and Chimeric Antigen Receptors

Abstract

A dvances in the field of cancer immunotherapy have enabled this therapeutic approach to enter the mainstream of modern cancer treatment. The ability of interleukin-2 (IL-2) administration to mediate complete, durable cancer regressions led to its approval by the US Food and Drug Administration for the treatment of patients with metastatic renal cancer in 1992 and metastatic melanoma in 1998. The ability of IL-2 to grow human T cells ex vivo led to the ability to generate tumor specific cells for the treatment of patients. Passive administration of anti-tumor T cells is referred to as adoptive cellular therapy (ACT). ACT has several advantages compared to other approaches to cancer immunotherapy. Large numbers of anti-tumor T cells can be grown in vitro and selected for high avidity against the desired antigen. In addition, the host can be manipulated prior to the administration of cells to provide a suitable microenvironment in the tumor. The first report of the use of tumor-infiltrating lymphocytes (TILs) for the treatment of patients was reported from the Surgery Branch, National Cancer Institute (NCI) in 1998. Extensive studies of TILs showed that cells with anti-tumor activity could be isolated from tumors derived from patients with melanoma, although using similar techniques TILs grown from most other cancer histologies did not appear to recognize tumor antigens. Further application of ACT led to the development of techniques to introduce anti-tumor T-cell receptors (TCRs) into autologous lymphocytes for use in therapy. Both conventional ab TCRs and chimeric antigen receptors (CARs) with anti-tumor specificity can be introduced into normal lymphocytes, providing them with anti-tumor activity. Clinical trials have been conducted targeting a variety of tumor histologies using this approach. In this review we will discuss