Identification of Target Antigens in Specific Immunotherapy for Renal Cell Carcinoma

Yoshihiro Komohara, Mamoru Harada, Yoshimi Arima, Shigetaka Suekane, Masanori Noguchi, Akira Yamada, Kyogo Itoh, Kei Matsuoka

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Purpose: Effective immunotherapy against renal cell carcinoma has not yet been established despite recent advances in specific immunotherapy for various malignancies. A plausible reason is limited information about target antigens of renal cell carcinoma. We searched for useful cancer antigens applicable to immunotherapy for renal cell carcinoma by examining antigen expression in renal cell carcinoma cell lines and testing the ability to induce renal cell carcinoma reactive cytotoxic T lymphocytes. Materials and Methods: mRNA expression of a panel of cancer associated antigens was examined using 5 renal cell carcinoma cell lines. Thereafter antigen derived peptides reported to induce cancer reactive cytotoxic T lymphocytes from human leukocyte antigen-A24+ patients with cancer were examined for their potential to induce cytotoxic T lymphocytes from peripheral blood mononuclear cells of human leukocyte antigen-A24+ patients with renal cell carcinoma. Results: Three candidate antigens, including multidrug resistance-associated protein 3, polycomb group protein enhancer of zeste homologue 2 and Her2/neu, were expressed in all 5 renal cell carcinoma cell lines. Six peptides derived from these antigens, including multidrug resistance-associated protein 3503-511, multidrug resistance-associated protein 31293-1302, polycomb group protein enhancer of zeste homologue 2291-299, polycomb group protein enhancer of zeste homologue 2735-743, Her2/neu342-350 and Her2/neu485-493, efficiently induced peptide specific and renal cell carcinoma reactive cytotoxic T lymphocytes from human leukocyte antigen-A24+ patients with renal cell carcinoma. Blocking and cold inhibition assays revealed that cytotoxicity against renal cell carcinoma depended on human leukocyte antigen class I restricted and peptide specific CD8+ T cells. Conclusions: This information could facilitate the development of effective immunotherapy against renal cell carcinoma.

Original languageEnglish
Pages (from-to)1157-1162
Number of pages6
JournalJournal of Urology
Volume177
Issue number3
DOIs
Publication statusPublished - 2007 Mar
Externally publishedYes

Keywords

  • T-lymphocytes
  • cancer vaccines
  • carcinoma
  • cytotoxic
  • kidney
  • renal cell

ASJC Scopus subject areas

  • Urology

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