Stimulating T Cells Against Cancer With Agonist Immunostimulatory Monoclonal Antibodies

Abstract

Elimination of cancer cells through antitumor immunity has been a long-sought after goal since Sir F. Macfarlane Burnet postulated the theory of immune surveillance against tumors in the 1950s. Finally, the use of immunotherapeutics against established cancer is becoming a reality in the past 5years. Most notable are the monoclonal antibodies (mAbs) directed against inhibitory T-cell receptors cytotoxic T lymphocyte antigen-4 and programmed death-1. The next generation of mAbs targeting T cells is designed to stimulate costimulatory receptors on T cells. Here we review the recent progress on these immunostimulatory agonist antibodies against the costimulatory receptors CD137, GITR, OX40, and CD27.

Keywords: Agonist; Cancer immunotherapy; Immunooncology; Immunostimulatory.

Figure 1:

Regulation of T cells by modulating TCR signals through co-stimulatory and co-inhibitory ligands and receptors.

Figure 2:

An immune synapse between effector T cells and an antigen-presenting cell (APC). Co-stimulatory ligands and receptors belonging to B7/CD28, and TNF/TNFR families are expressed on antigen presenting cells and T cells. The agonist monoclonal antibodies under clinical development can mimic the ligand to engage the co-stimulatory receptors.