CAR T cell therapy: newer approaches to counter resistance and cost

Rajesh Kumar Yadav; Asgar Ali; Santosh Kumar; Alpana Sharma; Basab Baghchi; Pritanjali Singh; Sushmita Das; Chandramani Singh; Sadhana Sharma

doi:10.1016/j.heliyon.2020.e03779

CAR T cell therapy: newer approaches to counter resistance and cost

Heliyon. 2020 Apr 16;6(4):e03779. doi: 10.1016/j.heliyon.2020.e03779. eCollection 2020 Apr.

Authors

Rajesh Kumar Yadav¹, Asgar Ali¹, Santosh Kumar¹, Alpana Sharma², Basab Baghchi³, Pritanjali Singh⁴, Sushmita Das⁵, Chandramani Singh⁶, Sadhana Sharma¹

Affiliations

¹ Department of Biochemistry, All India Institute of Medical Sciences, Patna, India.
² Department of Biochemistry, All India Institute of Medical Sciences, Delhi, India.
³ Department of Medical Oncology/Haematology, All India Institute of Medical Sciences, Patna, India.
⁴ Department of Radiotherapy, All India Institute of Medical Sciences, Patna, India.
⁵ Department of Microbiology, All India Institute of Medical Sciences, Patna, India.
⁶ Department of Community and Family Medicine, All India Institute of Medical Sciences, Patna, India.

Abstract

The genetically engineered Chimeric Antigen Receptor bearing T-cell (CAR T cell) therapy has been emerged as the new paradigm of cancer immunotherapy. However, recent studies have reported an increase in the number of relapsed haematological malignancies. This review provides newer insights into how the efficacy of CAR T cells might be increased by the application of new genome editing technologies, monitoring the complexity of tumor types and T cells sub-types. Next, tumor mutation burden along with tumormicroenvironment and epigenetic mechanisms of CAR T cell as well as tumor cell may play a vital role to tackle the cancer resistance mechanisms. These studies highlight the need to consider traditional cancer therapy in conjunction with CAR T cell therapy for relapsed or cases unresponsive to treatment. Of note, this therapy is highly expensive and requires multi-skill for successful implementation, which results in reduction of its accessibility/affordability to the patients. Here, we also propose a model for cost minimization of CAR T cell therapy by a collaboration of academia, hospitals and industry.

Keywords: Affordable; Biochemistry; CAR T cells; Cancer research; Cell biology; Clinical research; Combination therapy; Epigenetics; Genetics; Health sciences; Immunology; Immunotherapy; Molecular biology; Oncology; Proteins; Tumor mutation burden.

Publication types

Review