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Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient

Adoptive transfer of peripheral blood–derived, melanoma-reactive CD8(+) cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with anti-CTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a...

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Detalles Bibliográficos
Autores principales: Chapuis, Aude G., Lee, Sylvia M., Thompson, John A., Roberts, Ilana M., Margolin, Kim A., Bhatia, Shailender, Sloan, Heather L., Lai, Ivy, Wagener, Felecia, Shibuya, Kendall, Cao, Jianhong, Wolchok, Jedd D., Greenberg, Philip D., Yee, Cassian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925025/
https://www.ncbi.nlm.nih.gov/pubmed/27242164
http://dx.doi.org/10.1084/jem.20152021
Descripción
Sumario:Adoptive transfer of peripheral blood–derived, melanoma-reactive CD8(+) cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with anti-CTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a bolus of enhanced IL-21–primed polyclonal antigen-specific CTL combined with CTLA4 blockade might boost antitumor efficacy. In this first-in-human case study, the combination successfully led to a durable complete remission (CR) in a patient whose disease was refractory to both monoclonal CTL and anti-CTLA4. Long-term persistence and sustained anti-tumor activity of transferred CTL, as well as responses to nontargeted antigens, confirmed mutually beneficial effects of the combined treatment. In this first-in-human study, Chapuis et al. demonstrate that the combination of adoptive cellular therapy with CTLA4 blockade induces long-term remission in a melanoma patient resistant to both modalities administered serially and individually.