We generated and characterized a novel anti-idiotype antibody ganglidiomab and demonstrated activity against neuroblastoma.

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ZusammenfassungDie körperliche Untersuchung gewaltbetroffener, lebender Personen, aber auch in Fällen von Selbstbeschädigung, gehört zur täglichen Routine der rechtsmedizinischen Institute. Gleichwohl sind auch Ärzte anderer Fachrichtungen mit Opfern von fremder Gewalt konfrontiert. Die vorliegende Studie soll die Bedeutung einer gerichtsfesten Befunddokumentation bei Betroffenen häuslicher Gewalt außerhalb eines Strafverfahrens unterstreichen. In einer retrospektiven Querschnittsstudie wurden die Daten aus der rechtsmedizinischen Gewaltopferambulanz des Instituts für Rechtsmedizin Greifswald der Jahre 2011–2017 systematisch untersucht. Die Untersuchung ergab u. a. einen steigenden Anteil weiblicher Betroffener im Untersuchungsgut und als häufigsten Untersuchungsanlass den Verdacht auf häusliche Gewalt. Durch die jährlich steigenden Fallzahlen wird die Bedeutung der rechtsmedizinischen Gewaltopferambulanz für die umfassende Versorgung von Betroffenen von (häuslicher) Gewalt deutlich.

Purpose: Immunotherapy targeting disialoganglioside GD2 emerges as an important treatment option for neuroblastoma, a pediatric malignancy characterized by poor outcome. Here, we report the generation and characterization of ganglidiomab, a new anti-idiotype antibody to anti-GD2 antibodies of the 14.18 family for monitoring of clinical trials and the development of neuroblastoma vaccines. Experimental Design and Results: Balb/c mice were immunized with 14G2a and splenocytes 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 using “steady state” analysis. The sequences of framework- (FRs) and complementarity determining -regions (CDRs) of ganglidiomab were identified. Finally, we demonstrate 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 for immune monitoring of clinical trials with anti-GD2 antibodies and provide an important baseline for the development of anti-idiotype vaccines against malignancies expressing GD2. Citation Format: Holger N. Lode, Manuela Schmidt, Diana Seidel, Nicole Huebener, Diana Brackrock, Matthias Bleeke, Daniel Reker, Sven Brandt, Hans-Peter Mueller, Christiane Helm, Nikolai Siebert. Generation and characterization of anti-idiotype antibody ganglidiomab as GD2 surrogate for immunotherapy of neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A28.

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