Factors influencing antibody-mediated cytotoxicity during the immunotherapy of Rauscher-virus-induced myeloid leukemic cells.

Abstract

The present study was undertaken to determine the factors that influence antibody-mediated cytotoxicity during immunotherapy of virally transformed tumor cells. As model a Rauscher-virus-induced myeloid leukemic cell line of BALB/c origin (RMB-1) was used, which forms disseminated tumors, when inoculated intravenously in BALB/c mice. As previously reported, prolonged survival was obtained when tumor-bearing mice were treated in vivo with a single high dose of a tumor-specific IgG2a monoclonal antibody. This study shows that antibody-dependent cellular cytotoxicity is an important mechanism involved in tumor cell destruction. Since in vitro studies showed that peritoneal macrophages were capable of killing RMB-1 cells in the presence of tumor-specific monoclonal antibody and since in the tumors of mice treated with monoclonal antibody a high influx of macrophages was observed histologically, it is likely that macrophages play an important effector role in elimination of tumor cells. Successful therapy in C5-complement-deficient tumor-bearing mice suggests that complement-dependent cytotoxicity does not play a major role. In nude (T-cell-deficient) mice the therapeutic effect of tumor-specific IgG2a antibody was significantly less than in immunocompetent mice. Although infiltration analysis of tumors of treated and untreated mice showed equally low numbers of helper-T and suppressor/cytotoxic T-cells, the mortality studies of T-cell-deficient and immunocompetent mice indicate that T-cells play a substantial, auxiliary role during antibody-mediated, tumor destruction in our model.

• Authors: D Berends, T H van der Kwast, N J de Both, P G Mulder
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 28 Issue 2 Pg. 123-30 ( 1989) ISSN: 0340-7004 [Print] Germany
• PMID: 2783887 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Complement System Proteins

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antibody-Dependent Cell Cytotoxicity
• Cell Movement
• Complement System Proteins
• Cytotoxicity, Immunologic
• Female
• Immunologic Deficiency Syndromes (immunology, therapy)
• Leukemia, Experimental (immunology, pathology, therapy)
• Leukemia, Myeloid (immunology, pathology, therapy)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Mice, Nude
• Rauscher Virus (immunology)
• T-Lymphocytes (immunology)