Immune checkpoint inhibitors for cancer treatment

Abstract

During immune responses antigen-specific T cells are regulated by several mechanisms, including through inhibitory receptors and regulatory T cells, to avoid excessive or persistent immune responses. These regulatory mechanisms, which are called 'immune checkpoints', suppress T cell responses, particularly in patients with chronic viral infections and cancer where viral antigens or tumor antigens persist for a long time and contribute to T cell exhaustion. Among these regulatory mechanisms, cytotoxic T lymphocyte associated protein-4 ( CTLA-4) and programmed cell death 1 ( PD-1) are the most well-known receptors and both have been targeted for drug development. As a result, anti-CTLA-4 and anti-PD-1 ( or anti-PD-L1) antibodies were recently developed as immune checkpoint inhibitors for use in cancer treatments. In this review we describe several receptors that function as immunological checkpoints as well as the pharmaceuticals that target them.