Cultured Cancer Killers

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Science  17 Jun 2005:
Vol. 308, Issue 5729, pp. 1715
DOI: 10.1126/science.308.5729.1715c

Adoptive cell transfer represents a highly promising therapy for treating some forms of cancer. Isolated antitumor T cells are stimulated and expanded in culture before they are transferred back into the patient. Although this approach has yielded encouraging success in treating malignant melanoma, there is room for improvement.

Using a mouse tumor model, Gattinoni et al. observed that the duration of stimulation of antitumor T cells in culture had a negative impact on their subsequent ability to kill tumors in vivo. As expected, T cells that had undergone successive rounds of stimulation in vitro did acquire the capacity to kill tumor cell lines when tested in vitro, indicative of a persistently robust cytotoxic activity. However, the acquisition of an activated phenotype—including changes in the pattern of lymph node-homing receptors and responsiveness to the T cell growth factor interleukin-2—was accompanied by a reduced ability to replicate and to eradicate tumors upon subsequent transfer into mice. These results highlight important parameters to consider, as efforts to select and generate effective anti-tumor T cells for adoptive cellular immunotherapy are refined. — SJS

J. Clin. Invest. 115, 1616 (2005).

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