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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Published in:The Journal of experimental medicine Vol. 213; no. 7; p. 1133
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 27.06.2016
Subjects:
Adoptive Transfer - methods
CD8-Positive T-Lymphocytes - transplantation
CTLA-4 Antigen - immunology
Female
Humans
Interleukins - immunology
Male
Melanoma - immunology
Melanoma - therapy
Middle Aged
Neoplasm Metastasis
ISSN:1540-9538, 1540-9538
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Summary: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.
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ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20152021