Research ArticleLeukemia

T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia

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Science Translational Medicine  10 Aug 2011:
Vol. 3, Issue 95, pp. 95ra73
DOI: 10.1126/scitranslmed.3002842

Go CAR-Ts in the Fast Lane

As members of the body’s police force, cells of the immune system vigilantly pursue bad actors that harm healthy tissues, such as infection or cancer, and then try to deter dangerous activity. Researchers have long sought to harness the power of the immune system to fight cancers such as leukemia; however, targeting functional immune T cells to the tumor and maintaining these cells in patients remains challenging. Now, Kalos et al. have genetically modified T cells to express a chimeric antigen receptor (CAR) to yield so-called CAR T cells that specifically target chronic lymphocytic leukemia (CLL) (a B cell cancer). The designer T cells not only expanded, persisted, and attacked tumor cells after transfer into patients; they also mediated cancer remission. Innocent bystanders were also targeted, as reflected by decreased numbers of B cells and plasma cells and the development of hypogammaglobulinemia.

The CAR T cells used in this study expressed an antigen receptor that consists of antibody binding domains that bind in a restricted manner to the CD19 protein (which is found solely on normal B cells and plasma cells) attached to both a T cell–specific costimulatory domain and a T cell–specific intracellular signaling domain. The resulting chimeric receptor could activate T cells in response to CD19 in the absence of major histocompatibility complex restriction, allowing for much broader cellular targeting than is obtained with normal T cells. After transfer into three CLL patients, these CAR T cells expanded >1000-fold, persisted for more than 6 months, and eradicated CLL cells. Some of these CAR T cells persisted with a memory phenotype, which would allow them to respond more quickly and on a larger scale with a second exposure to CLL cells. Indeed, two of the three CLL patients who underwent the CAR T cell treatment had complete remission of their leukemia. Although this is early in the clinical study, these results highlight the potential for CAR-modified T cells to bring cancer therapy up to speed.


  • * These authors contributed equally to this work.

  • Citation: M. Kalos, B. L. Levine, D. L. Porter, S. Katz, S. A. Grupp, A. Bagg, C. H. June, T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia. Sci. Transl. Med. 3, 95ra73 (2011).

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