Jacobs Journal of Cancer Science and Research

Immunological Checkpoints: CD137 and LAG3 Receptors as a Target for Cancer Immunotherapy - Literature Review

*Michal Palonka
Department Of Oncology, Medical University Of Lublin, Medical University Of Lublin , Poland

*Corresponding Author:
Michal Palonka
Department Of Oncology, Medical University Of Lublin, Medical University Of Lublin , Poland
Email:m.palonka@gmail.com

Published on: 2018-10-29

Abstract

In recent years, the search for more efficient and less toxic anti-cancer therapies focuses on monoclonal antibodies targeting cells’ immune checkpoints. Stimulation of the immunological response against tumor cells is potentially safer than chemotherapy. However, the currently used anti-PD1, anti-PD-L1 or anti-CTLA4 antibodies are effective in a limited population of patients and also immunotherapy may induce autoimmune toxicity. The aim of this study was to present the latest information on anti-CD137 and anti-LAG3 monoclonal antibodies in anticancer therapy. The overview was made with the use of pubmed.com and clinicaltrials. gov databases, searched between the years 2000 – 2016. CD137 activating molecule provides signal to activation and proliferation of T-cells, recruitment of inflammatory cells, transformation of monocytes into macrophages and dendritic cells and the secretion of proinflammatory cytokines. LAG3 is an inhibiting protein constitutively expressed on surface of Treg cells and induced on CD4+, CD8+, NK cells, B cells and dendritic cells. It maintains the state of exhaustion of CD8+ T cells and reduces synthesis of many cytokines e.g. IFN-α. The results of the current studies indicate that the immunological checkpoints blockade or stimulation is the right approach towards the development of anticancer therapy.

Keywords

Cancer Immunotherapy; CD137; 4-1BB; LAG-3; Immunological Checkpoints

Introduction

An increase in cancer incidence observed for years prompts scientists to deal with the problem of carcinogenesis and immunological mechanisms involved in the pathogenesis and resistance to cancer treatment. Leading cancer therapies are based on the aim to irreversibly damage the DNA of cancer cells, either by ionizing radiation or chemotherapeutic agents. Unfortunately, the high toxicity and considerable damage to healthy tissue are the limitations of these methods of treatment. The search for new, more efficient and less toxic therapies focuses in recent years on the monoclonal antibodies against cells’ immune checkpoints. However, the currently used anti- PD1, anti-PD-L1 or anti-CTLA4 antibodies are effective in a limited population of patients and may induce autoimmune toxicity.