Assay for the detection of anti-idiotypic antibodies to monoclonal antibody B72.3

P. Ferroni, D. E. Milenic, J. Schlom, D. Colcher

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The administration of xenogenic monoclonal antibodies (MAbs) leads in many cases to a host immune response represented by the generation of antibodies that can be directed against allotypic, isotypic, and idiotypic determinants present on the xenogeneic MAb. Anti-idiotypic antibodies (Ab2s) can be detected by measuring their specific reactivity in sandwich assays using their ability to cross-link labeled Ab1 to Ab1 attached to a solid phase; however, when the MAb used for these studies reacts with a multideterminant tumor-associated antigen found in the circulation (e.g., TAG-72), the utility of these anti-idiotype assays may be limited. To determine the levels of anti-idiotypic antibodies that could be detected in patients undergoing MAb B72.3-based immunodiagnostic and immunotherapeutic protocols, we investigated the ability of a solid-phase sandwich radioimmunoassay (RIA) to detect anti-idiotypic antibodies raised against B72.3. Furthermore, to overcome the interference of circulating TAG-72 and/or antibodies to allotypic and isotypic determinants in the evaluation of an anti-idiotypic response, we developed a methodology using CC49-coated resin to adsorb the interfering molecules (CC49 is a second anti-TAG-72 MAb). Under the conditions established, all of the TAG-72 antigen was removed by adsorption with MAb CC49. Furthermore, since the treatment used an isotype-identical murine MAb, the binding due to the anti-mouse antibodies, other than the anti-idiotype, was completely abolished after a treatment with MAb CC49, leaving only the anti-idiotype component. Analysis of serum samples from patients who had received B72.3 that were positive for human anti-mouse antibodies in the B72.3 sandwich RIA, after the adsorption with CC49 resin, revealed the presence of a B72.3-binding component in 2 of 12 samples. The ability of the adsorbed sera to compete with an anti-B72.3-idiotype MAb for the binding sites present on the MAb B72.3 confirmed the anti-idiotypic nature of the component being detected in the patient sera.

Original languageEnglish
Pages (from-to)465-473
Number of pages9
JournalJournal of Clinical Laboratory Analysis
Volume4
Issue number6
DOIs
Publication statusPublished - 1991

Fingerprint

Anti-Idiotypic Antibodies
Assays
Monoclonal Antibodies
Antibodies
Adsorption
Radioimmunoassay
Immunoglobulin Allotypes
Resins
Serum
Heterophile Antibodies
Antigens
Neoplasm Antigens
B72.3 antibody
Tumors
Binding Sites
Molecules
tumor-associated antigen 72
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Assay for the detection of anti-idiotypic antibodies to monoclonal antibody B72.3. / Ferroni, P.; Milenic, D. E.; Schlom, J.; Colcher, D.

In: Journal of Clinical Laboratory Analysis, Vol. 4, No. 6, 1991, p. 465-473.

Research output: Contribution to journalArticle

Ferroni, P. ; Milenic, D. E. ; Schlom, J. ; Colcher, D. / Assay for the detection of anti-idiotypic antibodies to monoclonal antibody B72.3. In: Journal of Clinical Laboratory Analysis. 1991 ; Vol. 4, No. 6. pp. 465-473.
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