Unleash the power of the mighty T cells-basis of adoptive cellular therapy

Abstract

Adoptive cellular therapy (ACT) is an immunotherapy which involves the passive transfer of lymphocytes into a lymphodepleted host after ex vivo stimulation and expansion. Tumor-infiltrating lymphocytes (TILs) have shown objective tumor responses mainly restricted to melanoma and rely on a laborious manufacturing process. These limitations led to emergence of engineered cells, where normal peripheral blood lymphocytes are modified to express T cell receptors (TCRs) or chimeric antigen receptors (CARs) specific for tumor-associated antigens (TAAs). To date, CD19-targeted chimeric antigen receptor T (CAR T) cells have been the most extensively studied, showing complete and durable responses in B-cell malignancies. Antitumor responses with engineered T cells have often been accompanied by undesired toxicities in clinical trials including cytokine release syndrome (CRS) and neurotoxicity. In this review, we provide an overview of adoptive cellular strategies, early and ongoing clinical trials, adverse events and strategies to mitigate side effects and overcome limitations.

Keywords: Adoptive cellular therapy; Chimeric antigen receptor; Cytokine release syndrome; Lymphodepletion; Neurotoxicity; On-target toxicity; T cell receptor; Tumor-infiltrating lymphocyte.