Immunological properties of a single-chain fragment of the anti-idiotypic antibody ACA125

• Published in: Cancer Immunology, Immunotherapy Vol. 49; no. 4-5; pp. 186 - 192
• Main Authors: REINARTZ, S, WAGNER, U, GIFFELS, P, GRUENN, U, SCHLEBUSCH, H, WALLWIENER, D
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-07-2000; Springer-Verlag
• Subjects: Aluminum Hydroxide - pharmacology; Animals; Antibodies, Anti-Idiotypic - immunology; Antibodies, Monoclonal - immunology; Antibody Formation - immunology; Antibody Specificity; Antineoplastic agents; Biological and medical sciences; Dose-Response Relationship, Immunologic; Electrophoresis, Polyacrylamide Gel; Escherichia coli - metabolism; Female; Freund's Adjuvant - pharmacology; Immunoglobulin G - immunology; Immunotherapy; Medical sciences; Mice; Original; Ovarian Neoplasms - metabolism; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Antineoplastic agent; Intraperitoneal administration; Antigenic determinant; Rat; Vaccination; Fv-Fragment; Monoclonal antibody; Mimetism; Antigenicity; Immunotherapy; Humoral immunity; Single chain antibody; Immunization; Immune response; Tumor associated antigen; Rodentia; Vaccine; Incomplete antibody; Vertebrata; Mammalia; Treatment; Mouse; Animal; Antiidiotypic antibody; CA 125 antigen
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s002620000126

Vaccination with anti-idiotypic antibodies has been described as a promising concept for treatment of several malignant diseases. The murine monoclonal anti-idiotypic antibody ACA125 imitates a specific epitope of the tumor-associated antigen CA125 expressed by 80% of ovarian carcinomas. In the first clinical trial it could be shown that mAb ACA125 is able to elicit anti-anti-idiotypic antibodies (Ab3) with anti-CA125 specificity in patients with advanced ovarian cancer. In order to improve the capabilities of anti-idiotype vaccines we generated a genetically engineered single-chain fragment (scFv) ACA125 composed of heavy- and light-chain variable regions connected by a flexible linker. The antigenicity of scFv ACA125 was demonstrated by immunizing rats i.p. with scFv or complete mAb in complete/incomplete Freund's adjuvants (CFA/IFA) or precipitated by aluminium hydroxide. Negative control groups included applications of irrelevant mouse IgG or adjuvants alone. Anti-anti-idiotypic antibodies (Ab3) directed against the mAb ACA125 as well as specific anti-CA125 antibodies (Ab1') could be detected in all animals treated with scFv in CFA/IFA. Nevertheless, antibody titers were lower than when the complete mAb ACA 125 was used. Suprisingly, an increase of specificity could not be observed in scFv-immunized animals, which had been expected because of the lack of heavy- and light-chain constant regions that could raise rather unspecific anti-isotypic and anti-allotypic rat anti-(mouse Ig) antibodies (RAMA). In contrast, the RAMA responses detected in these rats were even stronger than those following immunization with complete mAb ACA125. In conclusion, the anti-idiotypic scFv ACA125 alone cannot improve the immunogenic features of the corresponding mAb, but provides a useful tool for the further development of genetic vaccines.