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Immunological circumvention of multiple organ metastases of multidrug resistant human small cell lung cancer cells by mouse-human chimeric anti-ganglioside GM2 antibody KM966.

Abstract
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.
AuthorsM Hanibuchi, S Yano, Y Nishioka, H Yanagawa, T Miki, S Sone
JournalClinical & experimental metastasis (Clin Exp Metastasis) Vol. 18 Issue 5 Pg. 353-60 ( 2000) ISSN: 0262-0898 [Print] Netherlands
PMID11467766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Cytokines
  • G(M2) Ganglioside
  • Doxorubicin
Topics
  • Animals
  • Antibodies, Monoclonal (pharmacology)
  • Antineoplastic Agents (pharmacology)
  • Carcinoma, Small Cell (drug therapy, immunology, secondary)
  • Cytokines (pharmacology)
  • Doxorubicin (pharmacology)
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm (immunology)
  • G(M2) Ganglioside (genetics, immunology)
  • Humans
  • Lung Neoplasms (drug therapy, immunology, secondary)
  • Male
  • Mice
  • Mice, SCID

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