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

Abstract

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.

• Authors: C E Touloukian, W W Leitner, P F Robbins, S A Rosenberg, N P Restifo
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 22 Pg. 8100-4 (Nov 15 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11719435 (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

Topics

• 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)