Prospects for CAR T cell immunotherapy in autoimmune diseases: clues from Lupus

ABSTRACT

Introduction

Medicine stands at the threshold of a new era heralded by the vast potential of cell engineering. Like advances made possible by genetic engineering, current prospects for purposeful control of cell functions through cell engineering may bring breakthroughs in the treatment of previously intractable diseases.

Areas covered

Engineering of cytotoxic T cells for expression of chimeric antigen receptors (CARs) instructs them to attack and destroy malignant cells and thus provides an exciting new approach in oncology. A decade of practical experience and first-in-human trials encourage the search for new and broader uses of CAR technology, including in autoimmune diseases.

Expert opinion

Systemic lupus erythematosus is an example of a broader category of autoimmune diseases, for which cell engineering will provide a powerful new therapeutic approach. This article describes different types of CAR T cell strategies that will provide new treatment options for patients with autoimmune diseases and replace conventional therapies.

KEYWORDS:

• Systemic lupus erythematosus
• chimeric antigen receptors
• cellular immunotherapy
• B cell depletion
• mouse models of autoimmune disease

Article highlights

• Autoimmune diseases are common and often life-threatening but generally lack effective treatments,

• B cells are at the center of autoimmune pathology in systemic lupus erythematosus and related diseases, but attempts to treat lupus with recombinant antibodies to CD20, a B cell marker, did not meet expectations.

• Cytotoxic T cells can be engineered to express chimeric antigen receptors (CARs) to CD19 on B cells, thus yielding sustained and highly effective cell-based immunotherapy that provides an improved approach to B cell depletion.

• Anti-CD19 CAR T cells are only one example of CAR T cells that show efficacy in animal models of autoimmune disease, and anti-CD19 CAR T cells were remarkably successful in their first use in a lupus patient.

• Scenarios are plausible and predictable, in which cell engineering will provide long-sought cures for severe, treatment-refractory autoimmune diseases.

This box summarizes key points contained in the article.

Declaration of interests

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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

The authors are funded by the Lupus Research Alliance and the University of Tennessee, University of Tennessee Health Science Center.