Immunological circumvention of multiple organ metastases of multidrug resistant human small cell lung cancer cells by mouse-human chimeric anti-ganglioside GM2 antibody KM966.
serum against SBC-3/DOX cells to a similar extent compared with parental SBC-3 cells. Pretreatment of human effector cells with various cytokines induced further enhancement of the KM966-dependent ADCC against SBC-3/DOX cells. Intravenous injection of SBC-3 or SBC-3/DOX cells into natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice developed metastases in multiple organs (liver, kidneys and lymph nodes). Interestingly, SBC-3/DOX cells produced metastases more rapidly than SBC-3 cells, suggesting more aggressive phenotype of SBC-3/DOX cells than their parental cells in vivo. Systemic treatment with KM966, given on days 2 and 7, drastically inhibited the formation of multiple-organ metastases produced by both SBC-3 and SBC-3/DOX cells, indicating that KM966 can eradicate metastasis by SCLC cells irrespective of MDR phenotype. These findings suggest that the mouse-human chimeric KM966 targets the GM2 antigen, and might be useful for the immunological circumvention of multiple-organ metastases of refractory SCLC.
Hanibuchi
M
M
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
Yano
S
S
Nishioka
Y
Y
Yanagawa
H
H
Miki
T
T
Sone
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary*; D016207:Cytokines / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D005678:G(M2) Ganglioside / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary*; D008297:Male; D051379:Mice; D016513:Mice, SCID
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016207:Cytokines; D005678:G(M2) Ganglioside; D004317:Doxorubicin