Helper T-Cell Responses and Clinical Activity of a Melanoma Vaccine With Multiple Peptides From MAGE and Melanocytic Differentiation Antigens

• Published in: Journal of clinical oncology Vol. 26; no. 30; pp. 4973 - 4980
• Main Authors: SLINGLUFFJR, Craig L, PETRONI, Gina R, MERRILL, Priscilla, FINK, Robyn, PATTERSON, James W, REHM, Patrice K, OLSON, Walter, CZARKOWSKI, Andrea, GROSH, William W, SMOLKIN, Mark, CHIANESE-BULLOCK, Kimberly A, NEESE, Patrice Y, DEACON, Donna H, NAIL, Carmel
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20.10.2008; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Differentiation - immunology; Antigens, Neoplasm - immunology; Biological and medical sciences; Cancer Vaccines - immunology; Cancer Vaccines - toxicity; Cell Proliferation; Dermatology; Female; gp100 Melanoma Antigen; Humans; Male; MART-1 Antigen; Medical sciences; Melanocytes - immunology; Melanoma; Melanoma - immunology; Melanoma - pathology; Melanoma - prevention & control; Membrane Glycoproteins - immunology; Middle Aged; Monophenol Monooxygenase - immunology; Neoplasm Proteins - immunology; Neoplasm Staging; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Skin Neoplasms - prevention & control; Skin Tests; T-Lymphocytes, Helper-Inducer - immunology; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Vitiligo - chemically induced; Cancer testis antigen; Cancerology; Immune response; Peptides; Melanoma associated antigen; Malignant melanoma; Helper cell; Vaccine; Malignant tumor; Cell differentiation; Biological activity; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2008.17.3161

A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel melanoma vaccine comprising six melanoma-associated peptides defined as antigenic targets for melanoma-reactive helper T cells. Source proteins for these peptides include MAGE proteins, MART-1/MelanA, gp100, and tyrosinase. Thirty-nine patients with stage IIIB to IV melanoma were vaccinated with this six-peptide mixture weekly at three dose levels, with a preceding phase I dose escalation and subsequent random assignment among the dose levels. Helper T-lymphocyte responses were assessed by in vitro proliferation assay and delayed-type hypersensitivity skin testing. Patients with measurable disease were evaluated for objective clinical response by Response Evaluation Criteria in Solid Tumors. Vaccination with the helper peptide vaccine was well tolerated. Proliferation assays revealed induction of T-cell responses to the melanoma helper peptides in 81% of patients. Among 17 patients with measurable disease, objective clinical responses were observed in two patients (12%), with response durations of 1 and 3.9+ years. Durable stable disease was observed in two additional patients for periods of 1.8 and 4.6+ years. Results of this study support the safety and immunogenicity of a vaccine comprised of six melanoma helper peptides. There is also early evidence of clinical activity.