Cancer Immunology, Immunotherapy

, Volume 49, Issue 4–5, pp 186–192 | Cite as

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

  • Silke Reinartz
  • Uwe Wagner
  • Patrick Giffels
  • Ursula Gruenn
  • Harald Schlebusch
  • Diethelm Wallwiener
ORIGINAL ARTICLE

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.

Key words Anti-idiotype vaccination scFv Immune responses Ovarian cancer 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Silke Reinartz
    • 1
  • Uwe Wagner
    • 1
  • Patrick Giffels
    • 1
  • Ursula Gruenn
    • 2
  • Harald Schlebusch
    • 2
  • Diethelm Wallwiener
    • 1
  1. 1.Center of Obstetrics and Gynecology, University of Tuebingen, Schleichstr. 4, 72076 Tübingen, Germany Tel.: +49-7071-2985380 Fax: +49-7071-295948DE
  2. 2.Center of Obstetrics and Gynecology, University of Bonn, GermanyDE

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