Monoclonal Antibodies for the Treatment of Cancer.

Abstract

The ability of cancer cells to evade the immune system is one of the most deadly characteristics of the majority of malignant tumours. Accordingly, the recent development of antibodies which target tumor cell evasion of immune checkpoints such as the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as the programmed cell death protein (PD-1) and the PD-1 ligand (PD-L1) has been a major and apparently highly effective approach in the treatment and/or eradication of a variety of highly malignant forms of cancers. The US Food and Drug Administration (FDA) has recently approved the application of lpilimumab (which targets CTLA-4) and pembrolizumab (targeting PD-1) for the treatment of advanced gastric cancer. Indeed, various checkpoint blockade antibodies have been approved or have been under clinical investigation. An indication of the renewed interest and importance of cancer immunotherapy is that James Allison was awarded the Lasker-DeBakey Clinical Research Award in 2015 for his discovery that antibody blockade of CTLA-4 enhances the immune response to cancer. Further, this discovery has stimulated the development of multiple immune checkpoint approaches to the treatment of cancer. In addition, a number of monoclonal antibodies (MAB) have been created to specifically target antigens on cancer cells and/or to selectively deliver radiotherapy to them. These immunotherapeutic approaches and advances will be reviewed in this article.