Immune Responses to a Class II Helper Peptide Epitope in Patients with Stage III/IV Resected Melanoma

• Published in: Clinical cancer research Vol. 10; no. 15; pp. 5004 - 5013
• Main Authors: WONG, Raymond, LAU, Roy, CHANG, Jenny, KUUS-REICHEL, Tina, BRICHARD, Vincent, BRUCK, Claudine, WEBER, Jeffrey
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2004
• Subjects: Age Factors; Alleles; Antigens, Neoplasm; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - chemistry; Cancer Vaccines - therapeutic use; CD3 Complex - biosynthesis; CD4 Antigens - biosynthesis; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Cell Proliferation; Dendritic Cells - cytology; Dendritic Cells - metabolism; Enzyme-Linked Immunosorbent Assay; Epitopes - chemistry; Female; Flow Cytometry; Granzymes; HLA Antigens - chemistry; HLA-DR Antigens - genetics; Humans; Immunotherapy - methods; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lipid A - analogs & derivatives; Lipid A - pharmacology; Lymphocytes - metabolism; Male; MART-1 Antigen; Medical sciences; Melanoma - metabolism; Melanoma - surgery; Melanoma - therapy; Microscopy, Fluorescence; Neoplasm Proteins - chemistry; Peptides - chemistry; Pharmacology. Drug treatments; Pilot Projects; Saponins - pharmacology; Serine Endopeptidases - chemistry; T-Lymphocytes - metabolism; Th1 Cells - immunology; Th2 Cells - immunology; Time Factors; Treatment Outcome; Tumors; Human; Immune response; Malignant tumor; Antigenic determinant; Peptides; Malignant melanoma
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0241

The importance of CD8 + cytolytic T cells for protection from viral infection and in the generation of immune responses against tumors has been well established. In contrast, the role of CD4 + T-helper cells in human infection and in cancer immunity has yet to be clearly defined. In this pilot study, we show that immunization of three resected, high-risk metastatic melanoma patients with a T-helper epitope derived from the melanoma differentiation antigen, melanoma antigen recognized by T cells-1, results in CD4 + T-cell immune responses. Immune reactivity to that epitope was detected by DR4-peptide tetramer staining, and enzyme-linked immunospot assay of fresh and restimulated CD4 + T cells from patients over the course of the 12-month vaccine regimen. The postvaccine CD4 + T cells exhibited a mixed T-helper 1/T-helper 2 phenotype, proliferated in response to the antigen and promiscuously recognized the peptide epitope bound to different human leukocyte antigen-DRβ alleles. For 1 DRβ1*0401 + patient, antigen-specific CD4 + T cells recognized human leukocyte antigen-matched antigen-expressing tumor cells, secreted granzyme B, and also exhibited cytolysis that was MHC class II-restricted. These data establish the immunogenicity of a class II epitope derived from a melanoma-associated antigen and support the inclusion of class II peptides in future melanoma vaccine therapies.