Aberrant expression and potency as a cancer immunotherapy target of inhibitor of apoptosis protein family, Livin/ML-IAP in lung cancer

Hiroyuki Hariu, Yoshihiko Hirohashi, Toshihiko Torigoe*, Hiroko Asanuma, Midori Hariu, Yasuaki Tamura, Katsuyuki Aketa, Chika Nabeta, Katsuya Nakanishi, Kenjiro Kamiguchi, Yoshinori Mano, Hiroshi Kitamura, Junichi Kobayashi, Tomohide Tsukahara, Noriharu Shijubo, Noriyuki Sato

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

CD8+ CTLs have an essential role in immune response against tumor. Although an increasing number of tumor-associated antigens that can be recognized by CTLs have been identified from human tumors, a limited number of tumor-associated antigens is known in lung cancer. In addition, because some of them are expressed in noncancerous tissues, there exist limitations in their application to tumor immunotherapy. Livin/ML-IAP is one of recently identified inhibitor of apoptosis protein (IAP) family, which is overexpressed in melanoma cells. In this report, we show that Livin/ML-IAP is aberrantly expressed in many lung cancer cell lines and primary lung cancer tissues, whereas it is not detectable in normal tissues, including lung by reverse transcription-PCR methods. To identify HLA-A24-restricted T-cell epitopes of Livin/ML-IAP, eight peptides were selected from the amino acid sequence of this protein and screened for their binding affinity to HLA-A24. It was revealed that Livin7 peptide (amino acid sequence, KWFPSCQFLL) had the highest affinity to HLA-A24. By stimulating peripheral blood lymphocytes of HLA-A24-positive lung cancer patients with Livin7 peptide in vitro, the peptide-specific CTLs were successfully induced from four of five patients with Livin/ ML-IAP-positive lung cancer but not from any of four patients without Livin/ML-IAP expression in their cancer tissues. Furthermore, the CTLs induced by Livin7 peptide showed cytotoxicity against Livin/ML-IAP+ lung cancer cell lines in an HLA-A24-restricted manner. Our data suggest that Livin/ML-IAP may be an excellent target antigen in immunotherapy for lung cancer and Livin? peptide may serve as a potent peptide vaccine for HLA-A*2402+/Livin + lung cancer patients.

Original languageEnglish
Pages (from-to)1000-1009
Number of pages10
JournalClinical Cancer Research
Volume11
Issue number3
StatePublished - 2005/02/01

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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