Adoptive T cell immunotherapy for cancer

Abstract

Harnessing the immune system to recognize and destroy tumor cells has been the central goal of anti-cancer immunotherapy. In recent years, there has been an increased interest in optimizing this technology in order to make it a clinically feasible treatment. One of the main treatment modalities within cancer immunotherapy has been adoptive T cell therapy (ACT). Using this approach, tumor-specific cytotoxic T cells are infused into cancer patients with the goal of recognizing, targeting, and destroying tumor cells. In the current review, we revisit some of the major successes of ACT, the major hurdles that have been overcome to optimize ACT, the remaining challenges, and future approaches to make ACT widely available.

Keywords: Adoptive T cell transfer; T cell engineering; cancer immunotherapy.

Figure 1.

T Cell Anti-Cancer Responses. Tumor-specific T cells (green) can recognize over-expressed antigens, neo-antigens derived from germline mutations, or so-called cancer germline antigens expressed de novo during carcinogenesis. However, several processes exist to suppress anti-cancer responses. T cell-intrinsic mechanisms such as loss of functionality and expression of checkpoint proteins (PD-1, CTLA-4) lead to T cell exhaustion. Tumor-intrinsic mechanisms include secretion of suppressive factors such as TGF-B, or expression or checkpoint ligands. Furthermore, tumors recruit suppressive cells such as regulatory T cells and tumor-associated macrophages that further inhibit T cell responses.

Figure 2.

The Process of Adoptive T Cell Immunotherapy. T cells are harvested either from tumor (tumor-infiltrating lymphocytes, TILs) or peripheral blood (peripheral blood lymphocytes, PBLs). TILs can be expanded non-specifically since they are preferentially tumor-specific prior to culture. In contrast, tumor specificity must be induced in PBLs, either through antigen-specific expansion or genetic engineering. After several weeks of expansion in culture, tumor-specific T cells can be reinfused into the cancer patient.