Immunological properties of a single-chain fragment of the anti-idiotypic antibody ACA125 |
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Authors: | Silke Reinartz Uwe Wagner Patrick Giffels Ursula Gruenn Harald Schlebusch Diethelm Wallwiener |
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Institution: | (1) Center of Obstetrics and Gynecology, University of Tuebingen, Schleichstr. 4, 72076 Tübingen, Germany Tel.: +49-7071-2985380 Fax: +49-7071-295948, DE;(2) Center of Obstetrics and Gynecology, University of Bonn, Germany, DE |
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Abstract: | 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 ACA125 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.
Received: 20 January 2000 / Accepted: 24 April 2000 |
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Keywords: | Anti-idiotype vaccination scFv Immune responses Ovarian cancer |
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