Monoclonal anti-idiotypic antibody mimicking a tumor-associated sialoglycoprotein antigen induces humoral immune response against human small-cell lung carcinoma.
We have previously described the tumor-associated sialoglycoprotein antigen sGP90-135 defined by the murine LAM8 MAb. The antigen is characterized by strong membrane expression in a proportion of small-cell carcinomas of the lung, but little or no expression on normal tissues of epithelial or neural origin or on blood cells. With the aim of obtaining anti-idiotypic antibodies which might be useful as surrogates for sGP90-135 in vaccination studies, LOU rats were immunized with LAM8 MAb and their spleen cells fused with Y3 rat myeloma cells. The LY8-229 hybrid was selected by an anti-idiotype competition radioimmunoassay on antigen-positive target cells. LY8-229 was shown to be a rat IgG1 with high specificity for LAM8 combining site. Solubilized small-cell carcinoma extract, as well as antibody SEN16, which recognizes the same tumor-associated antigen sGP90-135, selectively inhibited 125I-LY8-229 binding to LAM8. Serum from BALB/c mice and DA rats immunized with anti-idiotypic antibody LY8-229 showed reactivity with antigen-positive target cell lines, but not with antigen-negative control cell lines. The induction of a specific immune response in 2 different species by the anti-idiotypic antibody LY8-229 suggests that LY8-229 bears the internal image of the antigen sGP90-135 and that it might be a candidate for immunotherapy trials in cancer patients.
Barth
A
A
Department of Medicine, University Hospital of Zurich, Switzerland.
Waibel
R
R
Stahel
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000917:Antibody Formation; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D018288:Carcinoma, Small Cell / Q000276:immunology*; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012795:Sialoglycoproteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007130:Immunoglobulin Idiotypes; D012795:Sialoglycoproteins