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Selected Publication:

Zeng, Y; Fest, S; Kunert, R; Katinger, H; Pistoia, V; Michon, J; Lewis, G; Ladenstein, R; Lode, HN.
(2005): Anti-neuroblastoma effect of ch14.18 antibody produced in CHO cells is mediated by NK-cells in mice.
Mol Immunol. 2005; 42(11):1311-1319 FullText FullText_BOKU

Successful treatment of stage 4 neuroblastoma remains a major challenge in pediatric oncology. In order to improve the outcome, passive immunotherapy using human-mouse chimeric monoclonal anti-disialoganglioside GD2 antibody ch14.18 has been evaluated in early phase clinical trials with promising results in progressing stage 4 neuroblastoma patients. In preparation of European phase III clinical trial (HRNBL-I/ESIOP), the cell line used for production of ch14.18 was changed. Specifically, the plasmid encoding for ch14.18 antibody was recloned into CHO cells. Here, we report the in vitro and in vivo anti-neuroblastoma activity of antibody ch14.18 produced in CHO cells (ch14.18/CHO) compared to that of ch 14.18 manufactured from SP2/0 (ch 14.18/SP2/0) and NSO cells (ch14.18/NSO). First, we demonstrate identical binding of ch14.18/CHO to the nominal antigen disialoganglioside GD2 in vitro compared to ch14.18/SP2/0 and ch14.18/NSO. Binding was GD2-specific, since all precursor- and metabolite-gangliosides of GD2 tested were not recognized by chl4.18/CHO. Second, the functional properties of chl4.18/CHO were determined in complement-dependent cytotoxicity (CDC) and anti body-dependent cellular cytotoxicity (ADCC) reactions against GD2 positive neuroectodermal tumor cell lines in vitro. There was no difference in CDC mediated specific tumor cell lysis among the three different ch14.18 antibody preparations. Interestingly, chl4.18/CHO showed superior ADCC activity at low antibody concentrations. Third, the efficacy of ch 14.18/CHO was evaluated in the NXS2 neuroblastoma model in vivo. Importantly, the ch 14.18/CHO preparation was effective in suppression of experimental liver metastasis in this model. In vivo depletion of NK-cells completely abrogated this effect, suggesting that the mechanism involved in the ch 14.18/CHO induced anti-neuroblastoma effect is mediated by NK-dependent ADCC. (c) 2005 Elsevier Ltd. All rights reserved.
Authors BOKU Wien:
Katinger Hermann
Kunert Renate
Find related publications in this database (using NML MeSH Indexing)
Animals -
Antibodies, Monoclonal - biosynthesis
Antibody-Dependent Cell Cytotoxicity -
CHO Cells -
Cell Line, Tumor -
Child -
Cricetinae -
Cytotoxicity, Immunologic -
Gangliosides - immunology
Humans -
Immunization, Passive -
Killer Cells, Natural - immunology
Liver Neoplasms, Experimental - immunology
Mice -
Mice, Inbred A -
Neuroblastoma - immunology
Recombinant Fusion Proteins - biosynthesis

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