Recombinant human Hsp110-gp100 chaperone complex vaccine is nontoxic and induces response in advanced stage melanoma patients.

Autor:	Wach MM; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center.; Department of Surgery, University at Buffalo., Subjeck JR; Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Wang XY; Department of Human and Molecular Genetics, Virginia Commonwealth University.; Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia., Repasky E; Department of Immunology, Roswell Park Comprehensive Cancer Center., Matsuzaki J; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center., Yu H; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA., Wang C; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA., Fisher D; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center.; Department of Immunology, Roswell Park Comprehensive Cancer Center., Skitzki JJ; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center.; Department of Surgery, University at Buffalo.; Department of Immunology, Roswell Park Comprehensive Cancer Center., Kane JM 3rd; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center.; Department of Surgery, University at Buffalo.; Department of Immunology, Roswell Park Comprehensive Cancer Center.
Jazyk:	angličtina
Zdroj:	Melanoma research [Melanoma Res] 2022 Apr 01; Vol. 32 (2), pp. 88-97.
DOI:	10.1097/CMR.0000000000000796
Abstrakt:	Heat shock proteins (hsp) are intracellular chaperones that possess extracellular immunostimulatory properties when complexed with antigens. A recombinant Hsp110-gp100 chaperone complex vaccine showed an antitumor response and prolonged survival in murine melanoma. A phase Ib dose-escalation study of a recombinant human Hsp110-gp100 vaccine in advanced-stage melanoma patients was performed to evaluate toxicity, immunostimulatory potential and clinical response. Patients with pretreated, unresectable stage IIIB/C/IV melanoma received the chaperone complex vaccine in a dose-escalation protocol; three vaccinations over a 43-day-period. Tumor response, clinical toxicity and immune response were measured. Ten patients (eight female, median age 70 years) were enrolled and two patients had grade 1 adverse events; minor skin rash, hyperhidrosis and fever (no grade 2 or higher adverse events). Median progression-free survival was longer for lower vaccine doses as compared to the maximum dose of 180 mcg (4.5 vs. 2.9 months; P = 0.018). The lowest dose patients (30 and 60 mcg) had clinical tumor responses (one partial response, one stable disease). CD8+ T cell interferon-γ responses to gp100 were greater in the clinically responding patients. A pattern of B cell responses to vaccination was not observed. Regulatory T cell populations and co-stimulatory molecules including cytotoxic T-lymphocyte-associated protein 4 and PD-1 appeared to differ in responders versus nonresponders. A fully recombinant human Hsp110-gp100 chaperone complex vaccine had minimal toxicity, measurable tumor responses at lower doses and produced peripheral CD8+ T cell activation in patients with advanced, pretreated melanoma. Combination with currently available immunotherapies may augment clinical responses. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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