title: Combined IL-21-primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient.
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.
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
authors.forename: Aude G
authors.initials: AG
authors.lastname: Chapuis
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Washington Medical Center/FHCRC/Seattle Cancer Care Alliance, Seattle, WA 98109.
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
authors.forename: Ilana M
authors.initials: IM
authors.lastname: Roberts
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Washington Medical Center/FHCRC/Seattle Cancer Care Alliance, Seattle, WA 98109.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Washington Medical Center/FHCRC/Seattle Cancer Care Alliance, Seattle, WA 98109.
authors.forename: Shailender
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Sloan
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
authors.forename: Ivy
authors.initials: I
authors.lastname: Lai
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
authors.forename: Felecia
authors.initials: F
authors.lastname: Wagener
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
authors.forename: Kendall
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Cao
authors.affiliation: Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 100165.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.affiliation: 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.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
authors.affiliation: Program in Immunology, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109 cyee@mdanderson.org pgreen@u.washington.edu.
authors.forename: Cassian
authors.initials: C
authors.lastname: Yee
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D018414:CD8-Positive T-Lymphocytes / Q000637:transplantation*; D060908:CTLA-4 Antigen / Q000276:immunology*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000098546:Interleukin-21
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007378:Interleukins; D000098546:Interleukin-21