Vaccination with anti-idiotype antibody ganglidiomab mediates a GD 2 -specific anti-neuroblastoma immune response
作者： Holger N. Lode , Manuela Schmidt , Diana Seidel , Nicole Huebener , Diana Brackrock
DOI: 10.1007/S00262-013-1413-Y
关键词: Clone (B-cell biology) 、 Antibody 、 Immunization 、 Molecular biology 、 Immune system 、 Cell culture 、 Immunotherapy 、 Neuroblastoma 、 Virology 、 Chemistry 、 Antigen
摘要: 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 GD2-specific immune response with ganglidiomab, new anti-idiotype antibody to anti-GD2 antibodies 14.18 family. Ganglidiomab was generated following immunization Balb/c mice 14G2a, and splenocytes were harvested generate hybridoma cells. Clones screened ELISA mouse binding hu14.18. One positive clone selected purify characterize secreted IgG protein (κ, IgG1). This bound ch14.18/CHO, hu14.18, immunocytokines ch14.18-IL2 hu14.18-IL2 well NK-92 cells expressing scFv(ch14.18)-zeta receptor. Binding these nominal antigen lysis neuroblastoma NK-92-scFv(ch14.18)-zeta competitively inhibited proving surrogate function characteristics. The dissociation constants ganglidiomab from ranged 10.8 ± 5.01 53.5 ± 1.92 nM determined Biacore analyses. sequences framework complementarity-determining regions identified. Finally, demonstrated humoral after vaccination effective in mediating killing We novel activity against neuroblastoma.
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