The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma

Exp Mol Pathol. 2011 Feb;90(1):55-60. doi: 10.1016/j.yexmp.2010.10.001. Epub 2010 Oct 13.

Abstract

In our previous study, we demonstrated that a peptide derived from the novel centrosome residing protein Cep55/c10orf3 can be targeted by the cytotoxic T lymphocytes (CTLs) in peripheral blood mononuclear cells (PBMCs) of breast carcinoma patients. In this report, we evaluated the feasibility of cancer immunotherapy using Cep55/c10orf3 peptide for colorectal carcinoma (CRC). To evaluate the expression of Cep55/c10orf3 in CRC tissues, we performed immunohistochemical staining of using anti-Cep55/c10orf3 monoclonal antibody. Sixty-three percent cases showed weak positive for Cep55/c10orf3 in total 70 CRC cases. The Cep55/c10orf3 expression intention was collated with high histological grade of CRC. Thus, we hypothesized that Cep55/c10orf3 can also be the target of CTLs in CRC cases. We generated CTLs from PBMCs of human leukocyte antigen (HLA)-A24-positive colorectal carcinoma patients using HLA-A24-restricted Cep55/c10orf3 peptides. Two of 6 colorectal cancer patients were reactive for the Cep55/c10orf3_193(10) peptide, which was the only immunogenic peptide in breast carcinoma patients. CTL clone specific for Cep55/c10orf3_193(10) recognized and lysed HLA-A24 (+) and Cep55/c10orf3 (+) colorectal carcinoma cell lines. In addition, 1 of 6 colorectal carcinoma patients was reactive for the Cep55/c10orf3_402(11) and Cep55/c10orf3_283(12) peptides, but not for Cep55/c10orf3_193(10) with the ELISPOT assay. These observations suggest that the antigenic peptide repertoire presented by HLA-A24 in colorectal carcinoma might be different from that in breast carcinoma. Thus, these peptide vaccination peptide mixture of Cep55/c10orf3_193(10), Cep55/c10orf3_402(11) and Cep55/c10orf3_283(12) might be more effective than a single peptide in the treatment of colorectal carcinoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / therapeutic use*
  • Cell Cycle Proteins / immunology*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / therapy*
  • Feasibility Studies
  • Female
  • HLA-A Antigens / immunology
  • HLA-A Antigens / metabolism
  • HLA-A24 Antigen
  • Humans
  • Nuclear Proteins / immunology*
  • Nuclear Proteins / metabolism
  • Peptides / immunology*
  • Peptides / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Vaccines, Subunit / immunology
  • Vaccines, Subunit / therapeutic use*

Substances

  • Cancer Vaccines
  • Cell Cycle Proteins
  • Cep55 protein, human
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Nuclear Proteins
  • Peptides
  • Vaccines, Subunit