CAR T Cells for Solid Tumors: Armed and Ready to Go? : The Cancer Journal (original) (raw)

Reviews

Armed and Ready to Go?

From the *Bluebird Bio Inc., Boston, MA; and †Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.

The authors are supported by NIH grants 1R01CA173750-01 and P01 CA094237, CPRIT grant RP101335, Cookies for Kids’ Cancer, Alex Lemonade Stand Foundation, Dana Foundation, Sidney Kimmel Foundation, and James S McDonnell Foundation.

S.K. is an employee of Bluebird Bio. The Center for Cell and Gene Therapy (S.G.) has research collaboration with Celgene and Bluebird Bio. S.K. and S.G. have patent applications in the field of T cell and gene-modified T-cell therapy for cancer.

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.journalppo.com).

Reprints: Stephen Gottschalk, MD, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates St, Suite 1770, Houston, TX 77030. E-mail: [email protected].

Abstract

Chimeric antigen receptor (CAR) T cells face a unique set of challenges in the context of solid tumors. To induce a favorable clinical outcome, CAR T cells have to surmount a series of increasingly arduous tasks. First, they have to be made specific for an antigen whose expression clearly demarcates tumor from normal tissue. Then, they must be able to home and penetrate the desmoplastic stroma that surrounds the tumor. Once within the tumor, they must expand, persist, and mediate cytotoxicity in a hostile milieu largely composed of immunosuppressive modulators. Whereas a seemingly herculean task, all of the aforementioned requirements can potentially be met effectively through both intrinsic and/or extrinsic modifications of CAR T cells. In this review, we delineate the barriers imposed by solid tumors on CARs and strategies that have and should be undertaken to improve therapeutic response.