Research ArticleCancer Immunotherapy

Establishment of Antitumor Memory in Humans Using in Vitro–Educated CD8+ T Cells

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Science Translational Medicine  27 Apr 2011:
Vol. 3, Issue 80, pp. 80ra34
DOI: 10.1126/scitranslmed.3002207

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Memory that Keeps Going and Going

Senior scientists consoling their trainees about failed experiments tout the value of persistence. Yet, persistence is not only important for the scientist tirelessly pipetting at two in the morning, it is key for immunological memory as well. Melanoma is a malignant tumor of melanocytes, the pigment cells found in the skin. Advanced-stage melanoma has a poor prognosis, with patients on average surviving less than a year. A new promising therapy for advanced-stage melanoma patients harnesses the immune system to attack the tumor cells. In adoptive T cell therapy, cytotoxic cells specific for the tumor are transferred into patients, where they then traffic to and destroy the tumor cells. However, one limitation of this therapy is keeping the tumor-specific T cells alive in the patient, which has been largely unsuccessful in the absence of extensive treatment of the patient. Butler et al. now report a means to expand these T cells that allows them to persist in the absence of extra patient manipulation.

The authors use artificial antigen-presenting cells to turn antitumor T cells into memory T cells, which survive longer and respond more quickly than normal effector T cells. These artificial antigen-presenting cells express molecules that “costimulate” the T cells, resulting in T cells that both look and act like memory T cells in the culture dish. These educated tumor-specific cells were then introduced into patients with advanced-stage melanoma. These cells functioned as memory cells in the patients as well: persisting for long periods of time, homing to the tumor site, and demonstrating tumor-specific activation and function, all in the absence of further patient manipulation. Although this is an early clinical trial with a small number of patients, there is some indication that this treatment may have clinical benefit for patients with this devastating disease. Persistence, both of the T cells and the scientists running the study, has finally paid off.

Footnotes

  • Citation: M. O. Butler, P. Friedlander, M. I. Milstein, M. M. Mooney, G. Metzler, A. P. Murray, M. Tanaka, A. Berezovskaya, O. Imataki, L. Drury, L. Brennan, M. Flavin, D. Neuberg, K. Stevenson, D. Lawrence, F. S. Hodi, E. F. Velazquez, M. T. Jaklitsch, S. E. Russell, M. Mihm, L. M. Nadler, N. Hirano, Establishment of Antitumor Memory in Humans Using in Vitro–Educated CD8+ T Cells. Sci. Transl. Med. 3, 80ra34 (2011).

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