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J Exp Med. 2016 Jun 27;213(7):1133-9. doi: 10.1084/jem.20152021. Epub 2016 May 30.

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

Author information

1
Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
2
Division of Medical Oncology, Department of Medicine, University of Washington Medical Center/FHCRC/Seattle Cancer Care Alliance, Seattle, WA 98109.
3
Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 100165.
4
Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109 Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195 cyee@mdanderson.org pgreen@u.washington.edu.
5
Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109 cyee@mdanderson.org pgreen@u.washington.edu.

Abstract

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.

Comment in

PMID:
27242164
PMCID:
PMC4925025
DOI:
10.1084/jem.20152021
[Indexed for MEDLINE]
Free PMC Article

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