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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29-30
pubmed:dateCreated
2011-6-13
pubmed:abstractText
An optimal cancer vaccine should be able to induce highly potent, long-lasting, tumor-specific responses in the majority of the cancer patient population. One approach for achieving this is to use synthetic peptide vaccines derived from widely expressed tumor-associated antigens, that promiscuously bind multiple MHC class I and class II alleles. MUC1-SP-L (ImMucin, VXL100) is a 21mer peptide encoding the complete signal peptide domain of MUC1, a tumor-associated antigen expressed by over 90% of solid and non-solid tumors. MUC1-SP-L was predicted in silico to bind various MHC class I and MHC class II alleles, covering the majority of the Caucasian population. PBLs obtained from 13 naïve donors all proliferated, with a Stimulation Index (SI?2), to the MUC1-SP-L peptide, producing mixed CD4+ and CD8+ responses. Similar results were manifested by MUC1-SP-L in PBLs derived from 9 of 10 cancer patients with MUC1 positive tumors. CD4+ and CD8+ T cell populations exhibited CD45RO memory markers and secreted IFN-gamma and IL-2 following stimulation with MUC1-SP-L. These T cells also exhibited proliferation to the MUC1-SP-L inner 9mer epitopes and cytotoxicity against tumor cell lines expressing MUC1 and a concordant MHC class I allele. Cytotoxicity to MUC1-expressing human and murine tumors was shown also in T cells obtained from HLA-A2 transgenic mice and BALB/c syngeneic mice immunized with the MUC1-SP-L and GM-CSF. In an immunotherapy model, BALB/c mice inoculated with metastatic MUC1 transfected murine DA3 mammary tumor cells, exhibited significantly prolonged survival following vaccination with MUC1-SP-L. Our results indicate superior immunological and anti-tumor properties of MUC1-SP-L compared to previously published MUC1-derived epitopes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1873-2518
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4676-86
pubmed:meshHeading
pubmed-meshheading:21570434-Aged, pubmed-meshheading:21570434-Animals, pubmed-meshheading:21570434-Cancer Vaccines, pubmed-meshheading:21570434-Cell Proliferation, pubmed-meshheading:21570434-Cytotoxicity, Immunologic, pubmed-meshheading:21570434-Disease Models, Animal, pubmed-meshheading:21570434-Female, pubmed-meshheading:21570434-Histocompatibility Antigens, pubmed-meshheading:21570434-Humans, pubmed-meshheading:21570434-Immunotherapy, pubmed-meshheading:21570434-Leukocytes, Mononuclear, pubmed-meshheading:21570434-Male, pubmed-meshheading:21570434-Mice, pubmed-meshheading:21570434-Mice, Inbred BALB C, pubmed-meshheading:21570434-Mice, Transgenic, pubmed-meshheading:21570434-Middle Aged, pubmed-meshheading:21570434-Mucin-1, pubmed-meshheading:21570434-Neoplasms, pubmed-meshheading:21570434-Protein Binding, pubmed-meshheading:21570434-Rodent Diseases, pubmed-meshheading:21570434-Survival Analysis
pubmed:year
2011
pubmed:articleTitle
ImMucin: a novel therapeutic vaccine with promiscuous MHC binding for the treatment of MUC1-expressing tumors.
pubmed:affiliation
Vaxil BioTherapeutics Ltd., 13 Einstein Street, Weizmann Science Park, Nes-Ziona 74036, Israel.
pubmed:publicationType
Journal Article