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Immune responses to a class II helper peptide epitope in patients with stage III/IV resected melanoma.
Clin Cancer Res 2004; 10(15):5004-13CC

Abstract

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-DRbeta alleles. For 1 DRbeta1*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.

Authors+Show Affiliations

Department of Medicine, Keck/University of Southern California School of Medicine, Los Angeles, California 90089, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15297401

Citation

Wong, Raymond, et al. "Immune Responses to a Class II Helper Peptide Epitope in Patients With Stage III/IV Resected Melanoma." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 10, no. 15, 2004, pp. 5004-13.
Wong R, Lau R, Chang J, et al. Immune responses to a class II helper peptide epitope in patients with stage III/IV resected melanoma. Clin Cancer Res. 2004;10(15):5004-13.
Wong, R., Lau, R., Chang, J., Kuus-Reichel, T., Brichard, V., Bruck, C., & Weber, J. (2004). Immune responses to a class II helper peptide epitope in patients with stage III/IV resected melanoma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 10(15), pp. 5004-13.
Wong R, et al. Immune Responses to a Class II Helper Peptide Epitope in Patients With Stage III/IV Resected Melanoma. Clin Cancer Res. 2004 Aug 1;10(15):5004-13. PubMed PMID: 15297401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune responses to a class II helper peptide epitope in patients with stage III/IV resected melanoma. AU - Wong,Raymond, AU - Lau,Roy, AU - Chang,Jenny, AU - Kuus-Reichel,Tina, AU - Brichard,Vincent, AU - Bruck,Claudine, AU - Weber,Jeffrey, PY - 2004/8/7/pubmed PY - 2005/3/8/medline PY - 2004/8/7/entrez SP - 5004 EP - 13 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 10 IS - 15 N2 - 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-DRbeta alleles. For 1 DRbeta1*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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15297401/Immune_responses_to_a_class_II_helper_peptide_epitope_in_patients_with_stage_III/IV_resected_melanoma_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15297401 DB - PRIME DP - Unbound Medicine ER -