From monoclonal antibodies to chimeric antigen receptors for the treatment of human malignancies

Abstract

Monoclonal antibodies (mAbs) and their directly derived cell-based application known as chimeric antigen receptors (CARs) ensue from the need to develop novel therapeutic strategies that retain high anti-tumor activity, but carry reduced toxicity compared to conventional chemo- and radiotherapies. In this concise review article, we will summarize the application of antibodies designed to target antigens expressed by tumor cells, and the transition from these antibodies to the generation of CARs.

Figure 1

Schematic representation of a Chimeric Antigen Receptor. Panel A describes the generation of the scFv moiety from a mAb and its fusion with the -chain of the T-cell receptor. Panel B illustrates the native form of co-stimulatory endodomains. Panel C illustrates the schematic representation of 1^st, 2^nd, and 3^rd generation CARs including the intracytoplasmic domains of either CD28 or 4-1BB or the combination of CD28-OX40 or CD28-4-1BB.