4.7 Article

HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL

Journal

INTERNATIONAL JOURNAL OF CANCER
Volume 123, Issue 11, Pages 2616-2625

Publisher

WILEY
DOI: 10.1002/ijc.23823

Keywords

tumor immunology; cancer testis antigen; CDCA1; CTL; HLA-A2

Categories

Funding

  1. Ministry of Education, Science, Technology Sports and Culture (Japan) [17015035, 18014023]
  2. Ministry of Health, Labor and Welfare (Japan)
  3. Onco Therapy Science Co
  4. Grants-in-Aid for Scientific Research [17015035] Funding Source: KAKEN

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Toward the development of a novel cancer immunotherapy, we have previously identified several tumor-associated antigens (TAAs) and the epitopes recognized by human histocompatibility leukocyte (HLA)-A2/A24-restricted cytotoxic T lymphocyte (CTL). In this study, we tried to identify a TAA of lung cancer (I.,C) and its HLA-A2 restricted CTL. epitopes to provide a target antigen useful for cancer immunotherapy of LC. We identified it novel cancer testis antigen, cell division cycle associated gene I (CDCA1), overexpressed in nonsmall cell U: using a cDNA microarray analysis. The expression levels of CDCA1 were also increased in the majority of small cell LIE, cholangiocellular cancer, uninary bladder cancer and renal cell cancers. We used HLA-A2.1 transgenic mice to identify the HLA-A2 (A*0201)- restricted CDCA1 epitopes recognized by niouse CTL, and we investigated whether these peptides could induce CDCA1-reactive CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A2-positive donors and a NSCLC patient. Consequently, we found that the CDCA1(65-73) (YMMPVNSEV) peptide and CDCA1(351-359) (KLATAQFKI) peptide could induce peptide-reactive CTLs in HLA-A2.1 transgenic mice. fit HLA-A2 donors, in vitro stimulation of PBMC with these peptides could induce peptide-reactive CTLs which killed tumor cell lines endogenously expressing both HLA-A2 and CDCA1. As a result, CDCA1 is a novel cancer-testis antigen overexpressed in LC. cholangiocellular cancer, urinary bladder cancer and renal cell cancers, and CDCA1 may therefore be an ideal TAA useful for the diagnosis and immunotherapy of these cancers. (C) 2008 Wiley-Liss, Inc.

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