Erschienen in:
01.06.2013 | Original Article
Vaccination with anti-idiotype antibody ganglidiomab mediates a GD2-specific anti-neuroblastoma immune response
verfasst von:
Holger N. Lode, Manuela Schmidt, Diana Seidel, Nicole Huebener, Diana Brackrock, Matthias Bleeke, Daniel Reker, Sven Brandt, Hans-Peter Mueller, Christiane Helm, Nikolai Siebert
Erschienen in:
Cancer Immunology, Immunotherapy
|
Ausgabe 6/2013
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Abstract
Purpose
Immunotherapy targeting disialoganglioside GD2 emerges as an important treatment option for neuroblastoma, a pediatric malignancy characterized by poor outcome. Here, we report the induction of a GD2-specific immune response with ganglidiomab, a new anti-idiotype antibody to anti-GD2 antibodies of the 14.18 family.
Experimental design and results
Ganglidiomab was generated following immunization of Balb/c mice with 14G2a, and splenocytes were harvested to generate hybridoma cells. Clones were screened by ELISA for mouse antibody binding to hu14.18. One positive clone was selected to purify and characterize the secreted IgG protein (κ, IgG1). This antibody bound to anti-GD2 antibodies 14G2a, ch14.18/CHO, hu14.18, and to immunocytokines ch14.18-IL2 and hu14.18-IL2 as well as to NK-92 cells expressing scFv(ch14.18)-zeta receptor. Binding of these anti-GD2 antibodies to the nominal antigen GD2 as well as GD2-specific lysis of neuroblastoma cells by NK-92-scFv(ch14.18)-zeta cells was competitively inhibited by ganglidiomab, proving GD2 surrogate function and anti-idiotype characteristics. The dissociation constants of ganglidiomab from anti-GD2 antibodies ranged from 10.8 ± 5.01 to 53.5 ± 1.92 nM as determined by Biacore analyses. The sequences of framework and complementarity-determining regions of ganglidiomab were identified. Finally, we demonstrated induction of a GD2-specific humoral immune response after vaccination of mice with ganglidiomab effective in mediating GD2-specific killing of neuroblastoma cells.
Conclusion
We generated and characterized a novel anti-idiotype antibody ganglidiomab and demonstrated activity against neuroblastoma.