Novel approaches to promote CAR T-cell function in solid tumors

ABSTRACT

Introduction: Following recent breakthrough developments in the application of CAR T-cell treatments for hematologic cancers, the potential of this approach to achieve meaningful impact against solid tumors now warrants careful consideration.

Areas covered: Effective deployment of CAR T-cell immunotherapy for solid tumors has proven challenging to date, due to a series of formidable hurdles. The first of these is the paucity of safe targets for this highly potent, expensive and potentially toxic form of treatment. Compounding this, the tumor microenvironment (TME) constitutes a nexus of cellular and molecular elements that conspire to suppress effective immunological function at that site, corrupting the physiological reparative processes that operate during wound healing. These obstacles are considered with a view to addressing how next-generation CAR T-cell approaches may be effectively applied to different cancer types.

Expert opinion: A variety of novel synthetic biology and combinatorial strategies are being developed that can improve CAR T-cell specificity and combat immunosuppressive pathways found in the TME. In addition, recent advances in genome editing techniques are paving the way toward the production of universally applicable CAR T cells.

KEYWORDS:

• Chimeric antigen receptor
• solid tumor
• CAR T cell
• cancer

Article highlights

• CAR T cells have demonstrated clear efficacy in hematological cancers; however, treatment of solid tumors is more complex.

• Discovery of effective targets for CAR T-cell recognition is key when designing efficacious and safe therapies.

• The tumor microenvironment deploys various mechanisms to suppress CAR T cells, research into how these mechanisms work forms the basis for current advances in CAR T-cell development.

• To reduce cost, risk of production failure and variability in response rates production of universal CAR T-cell products is desirable.

This box summarizes key points contained in the article.

Declaration of interest

C Hull is a consultant to Leucid Bio. J Maher is Chief Scientific Officer of Leucid Bio. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was funded by the British Lung Foundation.