Therapeutic efficacy of mouse-human chimeric anti-ganglioside GM2 monoclonal antibody against multiple organ micrometastases of human lung cancer in NK cell-depleted SCID mice.
The development of distant metastases to multiple organs is a critical problem in the treatment of human lung cancer. In this study, we evaluated the therapeutic efficacy of a mouse-human chimeric anti-ganglioside GM2 (GM2) monoclonal antibody (MAb), KM966 against metastasis formation of GM2-positive human lung cancer cells inoculated intravenously (i.v.) into natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice. GM2-positive human small cell lung cancer (SCLC), SBC-3 cells (1 x 10(6)), injected through a tail vein into NK cell-depleted SCID mice, formed large number of metastatic colonies in the liver, kidneys and lymph nodes by 42 days after inoculation (day 42). KM966, but not control MAb, given on days 2 and 7, almost completely inhibited metastasis formation of SBC-3 cells in the liver, kidneys and lymph nodes in a dose-dependent fashion. Moreover, treatment with KM966 at advanced stages of metastasis (even from day 28) significantly suppressed multiple organ metastases of SBC-3 cells. The anti-metastatic effect of KM966 in vivo was mainly due to an antibody-dependent cell-mediated cytotoxicity (ADCC) reaction mediated by macrophages of the SCID mice. Our findings suggest that the mouse-human chimeric anti-GM2 MAb, KM966 may be useful for eradicating multiple organ micrometastases of lung cancer in humans.
Hanibuchi
M
M
Third Department of Internal Medicine, The University of Tokushima School of Medicine, Japan.
Yano
S
S
Nishioka
Y
Y
Yanagawa
H
H
Kawano
T
T
Sone
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D018288:Carcinoma, Small Cell / Q000556:secondary / Q000628:therapy*; D005678:G(M2) Ganglioside / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D005678:G(M2) Ganglioside