HM1.24 (CD317) is a novel target against lung cancer for immunotherapy using anti-HM1.24 antibody.
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.
Wang
Wei
W
Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan.
Nishioka
Yasuhiko
Y
Ozaki
Shuji
S
Jalili
Ali
A
Abe
Shinji
S
Kakiuchi
Soji
S
Kishuku
Masatoshi
M
Minakuchi
Kazuo
K
Matsumoto
Toshio
T
Sone
Saburo
S
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D018287:Carcinoma, Large Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D016066:Pleural Effusion, Malignant / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D014407:Tumor Cells, Cultured; D000074010:Bone Marrow Stromal Antigen 2
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2