Multi-targeted chimeric antigen receptor (car) t cell therapies as a new hope against glioblastoma; a systematic review

Abdolreza Esmaeilzadeh,1 abdolreza esmaeilzadeh,2,*

1. School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
2. Department of Immunology and Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran

Abstract

Introduction

Glioblastoma is the most invasive form of primary brain tumor with poor prognosis of about 12 to 15 months. conventional treatments including aggressive surgery, chemotherapy, and radiotherapy are accompanied by limited efficacy and multiple side effects. also, the immunosuppressive status of the glioblastoma promotes the immune evasion of this approach and leads to resistance of the tumor to treatment. thus, there is an urgent need for the development of novel treatment methods to fight glioblastoma. immunotherapy has recently been in the spotlight for glioblastoma treatment. adoptive cell therapy (act), manipulating and recruiting the lymphocytes and mononuclear cells of the patient’s blood, is one of the latest approaches in immunotherapy of glioblastoma that has recently shown promising results. chimeric antigen receptor (car) t cells are genetically engineered t cells that can be redirected against specific targets and exert their anti-tumor function after binding to their target

Methods

Pubmed, scopus, google scholar, elsevier, and embace were searched in english with the keywords: glioblastoma, immunotherapy, chimeric antigen receptor, and multi-target therapy from 2014 to october 2018. 20 articles were found based on our inclusion criteria, and 10 articles were selected and included in our study based on exclusion criteria

Results

Multiple studies have shown the safety and efficacy of car t cell therapies against glioblastoma; however, off-tumor toxicity and antigen heterogeneity still remain as the most important barriers. glioblastoma cells exhibit distinct levels of antigen expression. also, different sections of the tumor highly vary in the type of antigen they express. another obstacle that limits the efficacy of car t cell therapy is the antigen escape/loss after treatment. thus, it seems that targeting glioblastoma using multiple antigens could pave the way to improved efficacy and clinical outcome against this fatal brain cancer by overcoming the antigen heterogeneity, escape, and loss. this could also increase the anti-tumor activity of car t cells. to achieve this, novel strategies including dual and tandem cars have been developed.

Conclusion

Multi-targeted therapies have recently achieved much attention in immunotherapy of multiple diseases including glioblastoma. in this review, we aim to discuss the antigen expression profile and novel approaches of multi-targeted therapies of glioblastoma using car t cells. we would also provide novel suggestions for multi-targeted treatment of glioblastoma using car t cell therapy.

Keywords

Glioblastoma, immunotherapy, chimeric antigen receptor, multi-target therapy