Adoptive cellular therapies: the current landscape

Abstract

For many cancer types, the immune system plays an essential role in their development and growth. Based on these rather novel insights, immunotherapeutic strategies have been developed. In the past decade, immune checkpoint blockade has demonstrated a major breakthrough in cancer treatment and has currently been approved for the treatment of multiple tumor types. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) or gene-modified T cells expressing novel T cell receptors (TCR) or chimeric antigen receptors (CAR) is another strategy to modify the immune system to recognize tumor cells and thus carry out an anti-tumor effector function. These treatments have shown promising results in various tumor types, and multiple clinical trials are being conducted worldwide to further optimize this treatment modality. Most successful results were obtained in hematological malignancies with the use of CD19-directed CAR T cell therapy and already led to the commercial approval by the FDA. This review provides an overview of the developments in ACT, the associated toxicity, and the future potential of ACT in cancer treatment.

Keywords: Adoptive cell therapy; Chimeric antigen receptor; Immunotherapy; T cell receptor; Tumor-infiltrating lymphocytes.

Fig. 1

Schematic overview of the processes for adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL), ACT with T cell receptor (TCR) gene therapy and ACT with chimeric antigen receptor (CAR)-modified T cells. In ACT with TIL, tumor-resident T cells are isolated and expanded ex vivo after surgical resection of the tumor. Thereafter, the TILs are further expanded in a rapid expansion protocol (REP). Before intravenous adoptive transfer into the patient, the patient is treated with a lymphodepleting conditioning regimen. In ACT with genetically modified peripheral blood T cells, TCR gene therapy and CAR gene therapy can be distinguished. For both treatment modalities, peripheral blood T cells are isolated via leukapheresis. These T cells are then transduced by viral vectors to either express a specific TCR or CAR, respectively