Establishment of antitumor memory in humans using in vitro-educated CD8+ T cells
| Autor: | Philip Friedlander, Kristen E. Stevenson, F. Stephen Hodi, Sara Russell, Alla Berezovskaya, Elsa F. Velazquez, Michael T. Jaklitsch, Marisa Flavin, Genita Metzler, Osamu Imataki, Martin C. Mihm, Marcus O. Butler, Donna Neuberg, Lee M. Nadler, Donald P. Lawrence, Naoto Hirano, Mary M. Mooney, Makito Tanaka, Andrew P. Murray, Matthew I. Milstein, Linda Drury, Lisa L. Brennan |
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| Rok vydání: | 2011 |
| Předmět: |
Interleukin 2
Male Adoptive cell transfer Time Factors T cell Antigen-Presenting Cells CD8-Positive T-Lymphocytes Article Cell therapy Epitopes MART-1 Antigen NK-92 Antigens CD Cell Movement Immune Tolerance Cytotoxic T cell Medicine Humans CTLA-4 Antigen Antigen-presenting cell Melanoma Aged Aged 80 and over Interleukin-15 business.industry Antibodies Monoclonal General Medicine Middle Aged Adoptive Transfer medicine.anatomical_structure Phenotype Immunology Interleukin-2 Female business Immunologic Memory CD8 medicine.drug T-Lymphocytes Cytotoxic |
| Zdroj: | Science translational medicine. 3(80) |
| ISSN: | 1946-6242 |
| Popis: | While 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 anti-tumor T lymphocytes that not only retain specificity and function in vivo but also display an intrinsic capacity to survive. To date, adoptively transferred anti-tumor CD8+ T lymphocytes (CTL) have had limited life spans unless the host has been manipulated. To generate CTL that possess an intrinsic capacity to persist in vivo, we developed a human artificial antigen presenting cell system that can educate anti-tumor CTL to acquire both a central memory and effector memory phenotype as well as the capacity to survive in culture for prolonged periods of time. In the present report, we examined whether anti-tumor CTL generated using this system could function and persist in patients. Here, we showed that MART1-specific CTL, 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 CTL trafficked to the tumor, mediated biological and clinical responses, and established anti-tumor immunologic memory. Therefore, this approach may broaden the availability of adoptive cell therapy to patients both alone and in combination with other therapeutic modalities. |
| Databáze: | OpenAIRE |
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