Specific enhancement of the therapeutic effect of anti-idiotype antibodies on a murine B cell lymphoma by IL-2.
We have previously reported on the augmentation of monoclonal anti-Id antibodies by IL-2 in the therapy of a murine B cell lymphoma. The mechanism of this augmentation was through the expansion by IL-2 of effector cells mediating antibody-dependent cellular cytotoxicity. In this paper we explore the power of IL-2 to enhance anti-Id therapy on larger tumor burdens and at sites distant from the site of injection. The combination treatment was able to induce regression of established 1-cm s.c. tumors associated with microscopic metastatic tumor in lungs, liver, and spleen. Further studies into the mechanism of activity showed that IL-2 was unable to augment in vivo or in vitro tumor lysis by F(ab')2 fragments, thus emphasizing the importance of Fc interactions with antibody-dependent cellular cytotoxicity effector cells. FcR-bearing NK cells were increased in the peritoneum of IL-2-treated mice. The augmented therapeutic effect by the combination treatment was specific for tumor cells expressing the target Id, and non-specific cytotoxicity on Id-negative variants was not seen.
Berinstein
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Department of Medicine, Stanford University School of Medicine, CA 94305.
Starnes
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CO
Levy
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D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D001402:B-Lymphocytes; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology* / Q000627:therapeutic use; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008223:Lymphoma / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D011961:Receptors, Fc / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2; D011961:Receptors, Fc; C048844:anti-IgG