Nurturing a T Cell Brigade

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Science  14 Mar 2003:
Vol. 299, Issue 5613, pp. 1629
DOI: 10.1126/science.299.5613.1629b

The treatment of cancer by introducing tumor-fighting T cells into patients has seen some success for some types of malignancy. Generally, however, it has been difficult to produce enough such T cells and to maintain their in vitro reactivity within the patient.

In an attempt to overcome these shortcomings, Brentjens et al. transduced fresh human T cells with a chimeric antigen receptor (CAR) whose external domain recognizes CD19: a surface protein that is expressed in many B cell malignancies. In culture, these CAR+ T cells efficiently killed CD19-bearing tumor cells, retaining this activity even after extensive expansion. Infusing these expanded T cells into immunodeficient beige mice resulted in the eradication of a previously engrafted Burkitt lymphoma. Successful ex vivo activation, expansion, and in vivo survival of transduced T cells required the cytokine interleukin-15 and the costimulatory surface molecule CD80. Finally, T cells taken from patients with chronic lymphoid leukemia, after modification with the same CAR, were capable of killing autologous tumor cells in culture, hinting that translation of this work to the clinic might be feasible. — SJS

Nature Med.9, 279 (2003).

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