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Cancer Immunol Immunother (2009) 58:967976
DOI 10.1007/s00262-008-0612-4
ORIGINAL ARTICLE
HM1.24 (CD317) is a novel target against lung cancer for immunotherapy using anti-HM1.24 antibody
Wei Wang Yasuhiko Nishioka Shuji Ozaki Ali Jalili Shinji Abe Soji Kakiuchi Masatoshi Kishuku Kazuo Minakuchi Toshio Matsumoto Saburo Sone
Received: 24 February 2008 / Revised: 6 September 2008 / Accepted: 6 October 2008 / Published online: 1 November 2008 Springer-Verlag 2008
Abstract HM1.24 antigen (CD317) was originally identi-Wed as a cell surface protein that is preferentially overex-pressed on multiple myeloma cells. Immunotherapy using anti-HM1.24 antibody has been performed in patients with multiple myeloma as a phase I study. We examined the expression of HM1.24 antigen in lung cancer cells and the possibility of immunotherapy with anti-HM1.24 antibody which can induce antibody-dependent cellular cytotoxicity (ADCC). The expression of HM1.24 antigen in lung cancer cells was examined by Xow cytometry as well as immunohistochemistry using anti-HM1.24 antibody. ADCC was evaluated using a 6-h 51Cr release assay. EVects of various cytokines on the expression of HM1.24 and the ADCC were examined. The antitumor activity of anti-HM1.24 antibody in vivo was examined in SCID mice. HM1.24 antigen was detected in 11 of 26 non-small cell lung cancer cell lines (42%) and four of seven (57%) of small cell lung
cancer cells, and also expressed in the tissues of lung cancer. Anti-HM1.24 antibody eVectively induced ADCC in HM1.24-positive lung cancer cells. Interferon-[afii9826] and -[afii9828] increased the levels of HM1.24 antigen and the susceptibility of lung cancer cells to ADCC. Treatment with anti-HM1.24 antibody inhibited the growth of lung cancer cells expressing HM1.24 antigen in SCID mice. The combined therapy with IFN-[afii9826] and anti-HM1.24 antibody showed the enhanced antitumor eVects even in the delayed treatment schedule. HM1.24 antigen is a novel immunological target for the treatment of lung cancer with anti-HM1.24 antibody.
Keywords HM1.24 antigen Lung cancer Antibody-dependent cellular cytotoxicity Interferon Immunotherapy
Introduction
Lung cancer is the leading world-wide cause of cancer deaths. The care rate remains less than 15% despite improvements in surgery, radiotherapy, and chemotherapy [1, 2]. To prolong the survival of patients with lung cancer, the development of novel therapeutic modalities is of much interest. Recently, drugs targeting the epidermal growth factor receptor (EGFR) including geWtinib and erlotinib have been shown to be eVective...