Mining the melanosome for tumor vaccine targets: P.polypeptide is a novel tumor-associated antigen.

To identify novel, tumor-specific target antigens for vaccine development, we studied immune responses to P.polypeptide, an M(r) 110,000 integral melanosomal membrane protein associated with the Prader-Willi syndrome. Together with expressed sequence tag (EST) and serial analyses of gene expression (SAGE) library analyses, reverse transcription-PCR and Northern blotting verified that P.polypeptide expression was limited to melanoma and melanocytes. A single dominant epitope corresponding to positions 427-435 (IMLCLIAAV) was identified using allele-specific epitope forecasting combined with work in HLA-A*0201/K(b) transgenic mice. This epitope was then used to generate de novo human P.polypeptide-specific CD8+ T cells capable of recognizing P.polypeptide expressing human tumor cell lines in an HLA-A*0201-restricted fashion. Thus, P.polypeptide may be valuable in the creation of novel therapeutic anticancer vaccines.
AuthorsC E Touloukian, W W Leitner, P F Robbins, S A Rosenberg, N P Restifo
JournalCancer research (Cancer Res) Vol. 61 Issue 22 Pg. 8100-4 (Nov 15 2001) ISSN: 0008-5472 [Print] United States
PMID11719435 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • P.polypeptide
  • Peptides
  • RNA, Messenger
  • Animals
  • Antigen Presentation
  • Antigens, Neoplasm (biosynthesis, genetics, immunology)
  • CD8-Positive T-Lymphocytes (immunology)
  • Cancer Vaccines (immunology)
  • Epitopes (immunology)
  • Epitopes, T-Lymphocyte (immunology)
  • H-2 Antigens (immunology)
  • HLA-A Antigens (immunology)
  • HLA-A2 Antigen
  • Humans
  • Melanoma (genetics, immunology, metabolism)
  • Melanosomes (immunology, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptides (genetics, immunology)
  • RNA, Messenger (biosynthesis, genetics)

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