TCR-like antibodies in cancer immunotherapy

Abstract

Cancer immunotherapy has been regarded as the most significant scientific breakthrough of 2013, and antibody therapy is at the core of this breakthrough. Despite significant success achieved in recent years, it is still difficult to target intracellular antigens of tumor cells with traditional antibodies, and novel therapeutic strategies are needed. T cell receptor (TCR)-like antibodies comprise a novel family of antibodies that can recognize peptide/MHC complexes on tumor cell surfaces. TCR-like antibodies can execute specific and significant anti-tumor immunity through several distinct molecular mechanisms, and the success of this type of antibody therapy in melanoma, leukemia, and breast, colon, and prostate tumor models has excited researchers in the immunotherapy field. Here, we summarize the generation strategy, function, and molecular mechanisms of TCR-like antibodies described in publications, focusing on the most significant discoveries.

Keywords: Antibody; Immunotherapy; T cell receptor; TCR-like antibody; Tumor antigen.

Fig. 1

Schematics of T cell receptor (TCR) and TCR-like receptor. Both TCR and TCR-like antibodies recognize the peptide/MHC complex on the surface of tumor cells

Fig. 2

The molecular mechanisms of TCR-like antibodies against tumor cells. TCR-like antibodies mediate their anti-tumor effects through multiple mechanisms. (a) Conjugation with fluorescent reagents to detect the expression of the peptide/MHC complex on the surface of tumor cells. (b) Antibody-dependent cell-mediated cytotoxicity (ADCC) with NK cells. (c) Complement-dependent cytotoxicity (CDC) with complements. (d) Antibody-dependent cellular phagocytosis (ADCP) with microphages. (e) Direct induction of tumor cell apoptosis. (f) Conjugation with drugs or toxins. (g) Conjugation as a bi-specific T cell engager (BiTE). (h) CAR-T strategy. TCR-like: T cell receptor-like; MHC: major histocompatibility complex; MAC: membrane attack complex; FcγR: Fc gamma receptor; FcγR IIα: Fc gamma receptor II alpha