Establishment of antitumor memory in humans using in vitro-educated CD8+ T cells

Marcus O. Butler, Philip Friedlander, Matthew I. Milstein, Mary M. Mooney, Genita Metzler, Andrew P. Murray, Makito Tanaka, Alla Berezovskaya, Osamu Imataki, Linda Drury, Lisa Brennan, Marisa Flavin, Donna Neuberg, Kristen Stevenson, Donald Lawrence, F. Stephen Hodi, Elsa F. Velazquez, Michael T. Jaklitsch, Sara E. Russell, Martin MihmLee M. Nadler, Naoto Hirano

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Although advanced-stage melanoma patients have a median survival of less than a year, adoptive T cell therapy can induce durable clinical responses in some patients. Successful adoptive T cell therapy to treat cancer requires engraftment of antitumor T lymphocytes that not only retain specificity and function in vivo but also display an intrinsic capacity to survive. To date, adoptively transferred antitumor CD8+ T lymphocytes (CTLs) have had limited life spans unless the host has been manipulated. To generate CTLs that have an intrinsic capacity to persist in vivo, we developed a human artificial antigen-presenting cell system that can educate antitumor CTLs to acquire both a central memory and an effector memory phenotype as well as the capacity to survive in culture for prolonged periods of time. We examined whether antitumor CTLs generated using this system could function and persist in patients. We showed that MART1-specific CTLs, educated and expanded using our artificial antigen-presenting cell system, could survive for prolonged periods in advanced-stage melanoma patients without previous conditioning or cytokine treatment. Moreover, these CTLs trafficked to the tumor, mediated biological and clinical responses, and established antitumor immunologic memory. Therefore, this approach may broaden the availability of adoptive cell therapy to patients both alone and in combination with other therapeutic modalities.

Original languageEnglish
Article number80ra34
JournalScience Translational Medicine
Volume3
Issue number80
DOIs
Publication statusPublished - 27-04-2011

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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