Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer.

Abstract

Alpha-methylacyl-CoA racemase (AMACR) is an enzyme playing an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives. High expression levels of AMACR have been described in various cancers, including prostate cancer, colorectal cancer and kidney cancer. Because of its cancer-specific and frequent expression, AMACR could be an attractive target for cytotoxic T-lymphocyte (CTL)-based immunotherapy for cancer. In the present study, we examined the induction of AMACR-specific CTLs from prostate cancer patients' peripheral blood mononuclear cells (PBMCs) and determined HLA-A24-restricted CTL epitopes.RT-PCR and immunohistochemical analysis revealed that AMACR was strongly expressed in prostate cancer cell lines and tissues as compared with benign or normal prostate tissues. Four AMACR-derived peptides carrying the HLA-A24-binding motif were synthesized from the amino acid sequence of this protein and analyzed to determine their binding affinities to HLA-A24. By stimulating patient's PBMCs with the peptides, specific CTLs were successfully induced in 6 of 11 patients. The peptide-specific CTLs exerted significant cytotoxic activity against AMACR-expressing prostate cancer cells in the context of HLA-A24. Our study demonstrates that AMACR could become a target antigen for prostate cancer immunotherapy, and that the AMACR-derived peptides might be good peptide vaccine candidates for HLA-A24-positive AMACR-expressing cancer patients.

• Authors: Ichiya Honma, Toshihiko Torigoe, Yoshihiko Hirohashi, Hiroshi Kitamura, Eiji Sato, Naoya Masumori, Yasuaki Tamura, Taiji Tsukamoto, Noriyuki Sato
• Journal: Journal of translational medicine (J Transl Med) Vol. 7 Pg. 103 (Dec 09 2009) ISSN: 1479-5876 [Electronic] England
• PMID: 20003233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes
• HLA-A Antigens
• HLA-A24 Antigen
• Peptides
• Racemases and Epimerases
• alpha-methylacyl-CoA racemase

Topics

• Amino Acid Sequence
• Animals
• Cell Line, Tumor
• Cytotoxicity, Immunologic
• Epitopes
• HLA-A Antigens (genetics, metabolism)
• HLA-A24 Antigen
• Humans
• Immunotherapy (methods)
• Male
• Molecular Sequence Data
• Peptides (genetics, metabolism)
• Prostatic Neoplasms (enzymology, immunology, therapy)
• Protein Binding
• Racemases and Epimerases (genetics, metabolism)
• Tissue Distribution