Lymphoma regression induced by monoclonal anti-idiotypic antibodies correlates with their ability to induce Ig signal transduction and is not prevented by tumor expression of high levels of bcl-2 protein.
Custom-made monoclonal anti-idiotype antibodies (anti-Id MoAbs) have been tested as a treatment modality in 34 non-Hodgkin's lymphoma (NHL) patients. Partial or complete tumor remissions have been induced with this treatment in 68% of these patients. One mechanism by which anti-idiotype antibodies may have induced these tumor responses is via a direct antiproliferative effect on the tumor cells, resulting in apoptosis. Primary NHL cells do not proliferate well enough in vitro to test this hypothesis directly. Therefore, we studied the effect of anti-idiotype antibodies on signal transduction through the surface Ig receptor as measured by the induction of cellular protein tyrosine phosphorylation. To assess whether bcl-2 protein could protect lymphoma cells from death induced by anti-Id MoAb, we also measured the level of bcl-2 protein in the same tumor cells. We found a strong correlation between the ability of an anti-Id MoAb to induce an increase in tyrosine phosphorylation in vitro and its ability to induce a tumor regression in the patient. By contrast, the level of bcl-2 expressed by the tumor cells was not correlated with clinical response to anti-Id MoAb treatment.
Vuist
W M
WM
Department of Medicine, Stanford University Medical Center, CA 94305-5306.
Levy
R
R
Maloney
D G
DG
D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015870:Gene Expression; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011971:Receptors, Immunologic; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases