Development of the specific immunotherapy targeting to HM1.24 antigen against lung cancer

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HM 1.24 antigen (CD317) was originally identified as a cell surface protein that is preferentially overexpressed on multiple myeloma cells. 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 was examined by flow cytometry 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 15 of 33 lung cancer cell lines (45%). Anti-HM1.24 antibody effectively induced ADCC against HM1.24-positive lung cancer cells. Interferon-β and -y 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 SBC-5 lung cancer cel … More ls expressing HM1.24 antigen in SOD mice. The combined therapy with IFN-β and anti-HM1.24 antibody showed the enhanced antitumor effects even in the delayed treatment schedule.Next, we evaluated the and-tumor activity of mouse-human chimeric and humanized anti-HM1.24 monoclonal antibodies (mAbs) in vitro. Human peripheral blood lymphocytes and monocytes separated from mononuclear cells (PBMCs) were used as effector cells. Chimeric and humanized anti-1-1M1.24 mAbs effectively induced ADCC which is mediated more efficiently by lymphocytes than monocytes. The cytotoxic activity correlated with the level of HM1.24 expression on lung cancer cells. Natural Killer cells were identified as the major effector cells in ADCC. The treatment of lymphocytes with IL-2, IL-12 or IL-15 significantly increased the ADCC activity. PBMCs from patients with lung cancer induced a level of ADCC comparable to that induced by PBMCs from healthy donors.Collectively, HM1.24 antigen is a novel immunological target for the treatment of lung cancer with anti-HM1.24 antibody. Less