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CD28z CARs and Armored CARs

Pegram, Hollie J. PhD*; Park, Jae H. MD*; Brentjens, Renier J. MD, PhD*†‡

doi: 10.1097/PPO.0000000000000034
Reviews
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CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested in the clinic with very promising outcomes. However, limitations to CAR T cell therapy exist. These include lack of efficacy against some tumors, specific targeting of tumor cells without affecting normal tissue and retaining activity within the suppressive tumor microenvironment. Whereas promising clinical trials are in progress, preclinical development is focused on optimizing CAR design, to generate “armored CAR T cells,” which are protected from the inhibitory tumor microenvironment. Studies investigating the expression of cytokine transgenes, combination therapy with small molecule inhibitors, or monoclonal antibodies, are aimed at improving the antitumor efficacy of CAR T cell therapy. Other strategies aimed at improving CAR T cell therapy include using dual CARs and chemokine receptors to more specifically target tumor cells. This review will describe the current clinical data and some novel armored CAR T cell approaches for improving antitumor efficacy therapy.

From the *Department of Medicine, †Center for Cell Engineering, and ‡Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Centre, New York, NY.

The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Reprints: Renier J. Brentjens, MD, PhD, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, United States. E-mail: brentjer@mskcc.org.

© 2014 by Lippincott Williams & Wilkins