Innovation in BCMA CAR-T therapy: Building beyond the Model T

Rahul Banerjee; Sarah S Lee; Andrew J Cowan

doi:10.3389/fonc.2022.1070353

Innovation in BCMA CAR-T therapy: Building beyond the Model T

Front Oncol. 2022 Nov 24:12:1070353. doi: 10.3389/fonc.2022.1070353. eCollection 2022.

Authors

Rahul Banerjee^{1

2}, Sarah S Lee^{1

2}, Andrew J Cowan^{1

2}

Affiliations

¹ Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, United States.
² Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.

Abstract

Autologous chimeric antigen receptor T-cell (CAR-T) therapies targeting B-cell maturation antigen (BCMA) have revolutionized the field of multiple myeloma in the same way that the Ford Model T revolutionized the original CAR world a century ago. However, we are only beginning to understand how to improve the efficacy and usability of these cellular therapies. In this review, we explore three automotive analogies for innovation with BCMA CAR-T therapies: stronger engines, better mileage, and hassle-free delivery. Firstly, we can build stronger engines in terms of BCMA targeting: improved antigen binding, tools to modulate antigen density, and armoring to better reach the antigen itself. Secondly, we can improve "mileage" in terms of response durability through ex vivo CAR design and in vivo immune manipulation. Thirdly, we can implement hassle-free delivery through rapid manufacturing protocols and off-the-shelf products. Just as the Model T set a benchmark for car manufacturing over 100 years ago, idecabtagene vicleucel and ciltacabtagene autoleucel have now set the starting point for BCMA CAR-T therapy with their approvals. As with any emerging technology, whether automotive or cellular, the best in innovation and optimization is yet to come.

Keywords: BCMA CAR-T therapy; CAR-T; ciltacabtagene autoleucel; gamma secretase inhibitor; idecabtagene vicleucel; myeloma.

Publication types

Review