Human Leukocyte Antigen-a2-restricted Ctl Responses to Mutated Braf Peptides in Melanoma Patients.
From: The Wistar Institute, Philadelphia, PA 19104, USA.
Cancer research
- Publish Date: Mar 2006
- ISSN: 0008-5472
- Volume: 66
- Issue: 6
- Pages: 3287-93
- Medium: Print
- Language: English
- Citation (JAMA): Somasundaram Rajasekharan, Swoboda Rolf, Caputo Laura, et al. Human Leukocyte Antigen-a2-restricted Ctl Responses to Mutated Braf Peptides in Melanoma Patients.. Cancer Res. Mar 2006;66:3287-93
Abstract
Mutated BRAF (BRAF(V600E)) is a potential immunotherapeutic target for melanoma because of its tumor specificity and expression in the majority of these lesions derived from different patients. BRAF(V600E) is expressed intracellularly and not on the cell surface, therefore providing a target for T cells but not B cells. Demonstration of patients’ T cell responses to BRAF(V600E) would suggest the feasibility of active specific immunotherapy targeting the mutation in these patients. In the present study, BRAF(V600E) peptides with putative binding sites for human leukocyte antigen (HLA)-A2 were used to stimulate T lymphocytes of HLA-A2-positive melanoma patients. Four of five patients with BRAF(V600E)-positive lesions showed lymphoproliferative responses to BRAF(V600E) peptide stimulation. These responses were specific for the mutated epitope and HLA-A2 was restricted in three patients. Lymphocytes from these three patients were cytotoxic against HLA-A2-matched BRAF(V600E)-positive melanoma cells. None of the four patients with BRAF(V600E)-negative lesions and none of five healthy donors had lymphoproliferative responses specific for the mutated epitope. The high prevalence (approximately 50%) of HLA-A2 among melanoma patients renders HLA-A2-restricted BRAF(V600E) peptides attractive candidate vaccines for these patients.
Mesh Headings (Keywords): Binding Sites, Cell Line, Tumor, Cytokines, Epitopes, T-Lymphocyte, HLA-A Antigens, Humans, Immunotherapy, Adoptive, Lymphocyte Activation, Melanoma, Mutation, Peptide Fragments, Proto-Oncogene Proteins B-raf, T-Lymphocytes, Cytotoxic
Check for Full Text / PubMed Unique Identifier (PMID): 16540682
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.