Treatment of a murine B cell lymphoma with monoclonal antibodies and IL 2.
A transplantable murine B cell lymphoma was used to study combination therapy with anti-idiotype antibody and interleukin 2 (IL 2). Class-switched IgG2a and IgG2b antibodies were compared. A marked additive and sometimes synergistic effect was seen when IL 2 was combined with either IgG2a or IgG2b anti-idiotype antibodies. A synergistic effect was also seen when similar experiments were performed in nude mice. In vitro antibody-dependent cellular cytotoxicity (ADCC) assays showed that IL 2 enhanced antibody-mediated lysis by peritoneal cells exposed to IL 2 in vitro in a dose-related manner. Peritoneal cells harvested from mice treated in vivo with IL 2 contained an increased number of T cells and asialo GM+ natural killer cells, and also mediated enhanced ADCC. Depletion of natural killer cells with anti-asialo GM and complement resulted in a marked decrease in the antibody-dependent cytotoxicity mediated by these peritoneal cells. The mechanism of synergy between monoclonal antibody and IL 2 may be due to the direct or indirect activation of natural killer cells mediating ADCC.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D001402:B-Lymphocytes; D003131:Combined Modality Therapy; D005260:Female; D007074:Immunoglobulin G / Q000627:therapeutic use; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010529:Peritoneal Cavity / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013268:Stimulation, Chemical
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2