Wang Wei, Nishioka Yasuhiko, Ozaki Shuji, Jalili Ali, Abe Shinji, Kakiuchi Soji, Kishuku Masatoshi, Minakuchi Kazuo, Matsumoto Toshio, Sone Saburo
Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan.
Cancer Immunol Immunother. 2009 Jun;58(6):967-76. doi: 10.1007/s00262-008-0612-4. Epub 2008 Nov 1.
HM1.24 antigen (CD317) was originally identified as a cell surface protein that is preferentially overexpressed 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 flow cytometry as well as immunohistochemistry using anti-HM1.24 antibody. ADCC was evaluated using a 6-h (51)Cr release assay. Effects 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 effectively induced ADCC in HM1.24-positive lung cancer cells. Interferon-beta and -gamma 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-beta and anti-HM1.24 antibody showed the enhanced antitumor effects 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.
HM1.24抗原（CD317）最初被鉴定为一种在多发性骨髓瘤细胞上优先过度表达的细胞表面蛋白。使用抗HM1.24抗体的免疫疗法已在多发性骨髓瘤患者中作为一项I期研究进行。我们检测了肺癌细胞中HM1.24抗原的表达以及使用可诱导抗体依赖性细胞毒性（ADCC）的抗HM1.24抗体进行免疫治疗的可能性。通过流式细胞术以及使用抗HM1.24抗体的免疫组织化学检测肺癌细胞中HM1.24抗原的表达。使用6小时（51）铬释放试验评估ADCC。检测了各种细胞因子对HM1.24表达和ADCC的影响。在SCID小鼠中检测了抗HM1.24抗体在体内的抗肿瘤活性。在26个非小细胞肺癌细胞系中的11个（42%）以及7个小细胞肺癌细胞中的4个（57%）检测到HM1.24抗原，并且在肺癌组织中也有表达。抗HM1.24抗体在HM阳性肺癌细胞中有效诱导ADCC。干扰素-β和-γ增加了HM1.24抗原的水平以及肺癌细胞对ADCC的敏感性。用抗HM1.24抗体治疗可抑制SCID小鼠中表达HM1.24抗原的肺癌细胞的生长。即使在延迟治疗方案中，干扰素-β与抗HM1.24抗体的联合治疗也显示出增强的抗肿瘤作用。HM1.24抗原是用抗HM1.24抗体治疗肺癌的一个新的免疫靶点。
