Chimeric and humanized anti-HM1.24 antibodies mediate antibody-dependent cellular cytotoxicity against lung cancer cells.
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. The aim of this study was to evaluate the anti-tumor activity of mouse-human chimeric and humanized anti-HM1.24 monoclonal antibodies (mAbs) against lung cancer cells in vitro. Human peripheral blood lymphocytes and monocytes separated from mononuclear cells (PBMCs) were used as effector cells. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of chimeric and humanized anti-HM1.24 mAbs against lung cancer cells were determined by chromium-release assay. In some experiments, target or effector cells were pretreated with various cytokines. Chimeric and humanized anti-HM1.24 mAbs effectively induced ADCC against lung cancer cells 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 mediated by the anti-HM1.24 mAb. The treatment of lymphocytes or monocytes with IL-2, IL-12, IL-15, M-CSF, or IFN-gamma significantly increased the ADCC activity. Moreover, the culture of lung cancer cells with IFN-beta or IFN-gamma augmented their susceptibility to ADCC and CDC. PBMCs from patients with lung cancer induced a level of ADCC comparable to that induced by PBMCs from healthy donors. Chimeric or humanized anti-HM1.24 mAbs have potential as a new therapeutic tool in lung cancer, and in combination with interleukins and interferons, could be useful for enhancing ADCC.
Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Wei
W
Wang
Yasuhiko
Y
Nishioka
Shuji
S
Ozaki
Ali
A
Jalili
Vinod Kumar
VK
Verma
Masaki
M
Hanibuchi
Shinji
S
Abe
Kazuo
K
Minakuchi
Toshio
T
Matsumoto
Saburo
S
Sone
D000911:Antibodies, Monoclonal / Q000737:chemistry; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000737:chemistry*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy*; D008214:Lymphocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D000074010:Bone Marrow Stromal Antigen 2
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D058851:GPI-Linked Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2