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Review
. 2018 Dec 4;6(1):137.
doi: 10.1186/s40425-018-0460-5.

Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance

Michael M Boyiadzis  1 , Madhav V Dhodapkar  2 , Renier J Brentjens  3 , James N Kochenderfer  4 , Sattva S Neelapu  5 , Marcela V Maus  6 , David L Porter  7 , David G Maloney  8 , Stephan A Grupp  7   9 , Crystal L Mackall  10 , Carl H June  7 , Michael R Bishop  11   12
Affiliations
Review

Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance

Michael M Boyiadzis et al. J Immunother Cancer. .

Abstract

Chimeric Antigen Receptor (CAR) T cell therapies - adoptive T cell therapies that have been genetically engineered for a new antigen-specificity - have displayed significant success in treating patients with hematologic malignancies, leading to three recent US Food and Drug Administration approvals. Based on the promise generated from these successes, the field is rapidly evolving to include new disease indications and CAR designs, while simultaneously reviewing and optimizing toxicity and management protocols. As such, this review provides expert perspective on the significance and clinical considerations of CAR T cell therapies in order to provide timely information to clinicians about this revolutionary new therapeutic class.

Keywords: Axicabtagene ciloleucel; Chimeric antigen receptor; Leukemia; Lymphoma; Tisagenlecleucel.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

JNK has received research funding from Kite Pharma and Bluebird Bio. He has also received royalties from intellectual property interests through Kite Pharma, Bluebird Bio, and Novartis. SSN has received research funding from Kite Pharma, Merck, Bristol-Myers Squibb, Cellectis, Poseida, Acerta, Karus. He has also served as a consultant for Kite Pharma, Novartis, Unum Therapeutics, Celgene, and Merck. MVM has received consulting fees from Novartis, Juno, and Kite Pharma, and has intellectual property interests through the University of Pennsylvania. DLP has received research funding from Novartis, and has served on advisory boards for Kite Pharma and Bellicum. In addition, Dr. Porter reports intellectual property interests through the University of Pennsylvania, and that his spouse is employed by Genentech. DGM has received research funding from Juno Therapeutics and Kite Pharma, and has received personal fees for serving on the scientific advisory board from Celgene, BioLink RX, Eureka, Roche/Genentech, Kite Pharma/Gilead, Novartis, Bristol-Myers Squibb, Immunogen, and Seattle Genetics. In addition, he has a pending patents related to cellular therapies. SAG has served on the SCC for Novartis and on the scientific advisory board for TCR2 Therapeutics, Eureka Therapeutics, Adaptimmune, and Cellectis/Servier. CLM has received personal fees for serving on the scientific advisory board for Unum Therapeutics, Glaxo-Smith Kline, Adaptimmune, Servier/Pfizer, Vor Pharmaceuticals, Apricity Health, and Allogene. In addition, she has intellectual property interests through Juno Therapeutics, as well as multiple pending patents related to CAR T therapies. CHJ has received research funding and has intellectual property interests through Novartis. He is also a scientific founder of Tmunity Therapeutics and reports stock holdings. MRB has served as a clinical investigator and advisory board member for Novartis and Juno Therapeutics. He has also served as a clinical investigator, advisory board member, and on the Speakers Bureau with honoraria for Kite Pharma. MMB, MVD, and RJB declare no competing interests.

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Figures

Fig. 1
Fig. 1
Chimeric Antigen Receptor (CAR) design across generations. First generation Chimeric Antigen Receptors (CARs) include an extracellular antigen-binding domain and an intracellular T cell activation domain, commonly CD3ζ or FcεRIγ. Second generation CARs built upon first generation constructs by including an intracellular costimulatory domain, commonly 4-1BB or CD28, incorporated into the FDA approved CAR T therapies tisagenlecleucel and axicabtagene ciloleucel, respectively. Costimulatory domains help enhance CAR T cell cytotoxicity and proliferation compared to first generation designs. Third generation CARs include multiple costimulatory domains, primarily to increase CAR T cell proliferation and persistence
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