Humanized anti-ganglioside GM2 antibody is effective to induce antibody-dependent cell-mediated cytotoxicity in mononuclear cells from lung cancer patients.
Ganglioside GM2 is one of the major gangliosides expressed on the cell surface of human tumors including lung cancer. We have previously reported that a mouse-human chimeric monoclonal antibody (mAb), KM966, against GM2 promotes the lysis of lung cancer cells by human blood mononuclear cells (MNC) of healthy donors. In this study, we examined antibody-dependent cell-mediated cytotoxicity (ADCC) of MNC, using KM966 mAb and its humanized counterpart, KM8969, in 16 lung cancer patients and 18 control patients. The ADCC activity was assessed by 4-h (51)Cr release from GM2 positive SBC-3 small cell lung cancer cells. MNC from lung cancer patients exhibited similar ADCC activity to those from control patients when KM966 and KM8969 were used as mAb. Moreover, effective ADCC activity was observed even in MNC from advanced lung cancer patients. These observations suggest the potential activity of humanized anti-GM2 mAb (KM8969), as well as chimeric KM966, in biological therapy for lung cancer patients.
Third Department of Internal Medicine, The University of Tokushima School of Medicine, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan.
P
P
Parajuli
H
H
Yanagawa
M
M
Hanibuchi
E
E
Takeuchi
T
T
Miki
S
S
Yano
S
S
Sone
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000378:metabolism; D016022:Case-Control Studies; D002857:Chromium / Q000378:metabolism; D005678:G(M2) Ganglioside / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D008875:Middle Aged; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002857:Chromium; D005678:G(M2) Ganglioside