A Randomized Phase II Trial of Multiepitope Vaccination with Melanoma Peptides for Cytotoxic T Cells and Helper T Cells for Patients with Metastatic Melanoma (E1602)

• Published in: Clinical cancer research 2013-08, Vol.19 (15), p.4228-4238
• Main Authors: SLINGLUFF, Craig L, LEE, Sandra, FENGMIN ZHAO, CHIANESE-BULLOCK, Kimberly A, OLSON, Walter C, BUTTERFIELD, Lisa H, WHITESIDE, Theresa L, LEMING, Philip D, KIRKWOOD, John M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Dermatology; Female; Freund's Adjuvant; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Humans; Kaplan-Meier Estimate; Lipids; Male; Medical sciences; Melanoma - drug therapy; Melanoma - immunology; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Metastasis - drug therapy; Neoplasm Metastasis - immunology; Neoplasm Staging; Peptides - administration & dosage; Pharmacology. Drug treatments; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Tetanus - metabolism; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Vaccination; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-13-0002

This multicenter randomized trial was designed to evaluate whether melanoma helper peptides augment cytotoxic T lymphocyte (CTL) responses to a melanoma vaccine and improve clinical outcome in patients with advanced melanoma. One hundred seventy-five patients with measurable stage IV melanoma were enrolled into 4 treatment groups, vaccinated with 12 MHC class I-restricted melanoma peptides to stimulate CTL (12 MP, group A), plus a tetanus peptide (group B), or a mixture of 6 melanoma helper peptides (6 MHP, group C) to stimulate helper T lymphocytes (HTL), or with 6 melanoma helper peptide (6 MHP) alone (group D), in incomplete Freund's adjuvant plus granulocyte macrophage colony-stimulating factor. CTL responses were assessed using an in vitro-stimulated IFN-γ ELIspot assay, and HTL responses were assessed using a proliferation assay. In groups A to D, respectively, CTL response rates to 12 melanoma peptides were 43%, 47%, 28%, and 5%, and HTL response rates to 6 MHP were in 3%, 0%, 40%, and 41%. Best clinical response was partial response in 7 of 148 evaluable patients (4.7%) without significant difference among study arms. Median overall survival (OS) was 11.8 months. Immune response to 6 MHP was significantly associated with both clinical response (P = 0.036) and OS (P = 0.004). Each vaccine regimen was immunogenic, but MHPs did not augment CTL responses to 12 melanoma peptides. The association of survival and immune response to 6 MHP supports further investigation of helper peptide vaccines. For patients with advanced melanoma, multipeptide vaccines should be studied in combination with other potentially synergistic active therapies.