Harnessing the immune system against cancer: current immunotherapy approaches and therapeutic targets

Abstract

Cancer immunotherapy is a rapidly evolving concept that has been given the tag "fifth pillar" of cancer therapy while radiation therapy, chemotherapy, surgery and targeted therapy remain the other four pillars. This involves the stimulation of the immune system to control tumor growth and it specifically targets the neoplastic cells rather than the normal cells. Conventional chemotherapy has many limitations which include drug resistance, recurrence of cancer and severe adverse effects. Immunology has made major treatment breakthroughs for several cancers such as colorectal cancer, prostate cancer, breast cancer, lung cancer, liver cancer, kidney cancer, stomach cancer, acute lymphoblastic leukaemia etc. Currently, therapeutic strategies harnessing the immune system involve Checkpoint inhibitors, Chimeric antigen receptor T cells (CAR T cells), Monoclonal antibodies, Cancer vaccines, Cytokines, Radio-immunotherapy and Oncolytic virus therapy. The molecular characterization of several tumor antigens (TA) indicates that these TA can be utilized as promising candidates in cancer immunotherapy strategies. Here in this review, we highlight and summarize the different categories of emerging cancer immunotherapies along with the immunologically recognized tumor antigens involved in the tumor microenvironment.

Keywords: CAR T cells; CTLA-4; Cancer immunotherapy; Cancer vaccines; Checkpoint inhibitor; Cytokines; Monoclonal antibodies; Oncolytic viruses; PD-1; PD-L1.

Fig. 1

Working mechanism of CTLA-4 and PD-1 on cancer cells. The activation of T cells is mediated by the interaction of the T cell receptor and the CD28 receptor with class II major histocompatibility complex and B7 co-stimulatory molecule located on the antigen-presenting cells. The interaction of CTLA-4 with the B7 molecule delivers an inhibitory signal, effectively checked by CTLA-4 inhibitors. On the other hand, the negative regulation of T cells resulting from PD-1/PD-L1 interaction between T cells and tumor cells is prevented by PD-1/PD-L1 inhibitors

Fig. 2

Generation of CAR-T Cells for immunotherapy. One form of adoptive cell therapy is CAR (Chimeric antigen receptors) T cell therapy. It is an accepted treatment procedure for both lymphomas and leukaemias. CAR T cell therapy is considered as a type of adoptive immune cell therapy where T cells are collected from a patient’s tumor sample, taken to a laboratory where the T-cell receptor is incorporated with tumor antigen-specific antibody receptor to get chimeric antigen receptor T (CAR T) cells. Nowadays MUC 1 and Glypican 3 targeting CAR-T cells are under clinical trial for different cancers