Bispecific GD2xB7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma

Erbe, A.; Feils, A.; Reinthaler, S.; Hampton, A.; Rosenkrans, Z.; Medina Guevara, Y.; Felder, M.; Wiwczar, J.; Gerhardt, D.; Bercher, M.; Wenke, B.; Haertle, C.; Heck, M.; Heimstreet, K.; Frankel, E.; Nielsen, M.; Spiegelman, D.; Tsarovsky, N.; Zaborek, J.; Rakhmilevich, A.; Hank, J.; Aluicio-Sarduy, E.; Engle, J.; Davis, J.; Glaser, B.; Subbotin, V.; Green, R.; Hernandez, R.; Hammer, B.; Sondel, P.

doi:10.64898/2026.09.21.753180

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bioRxiv · 10.64898/2026.09.21.753180

Bispecific GD2xB7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma

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Abstract

The current treatment regimen for neuroblastoma involves immunotherapy, including a monoclonal antibody that recognizes disialoganglioside (GD2), expressed at high levels on neuroblastoma. GD2 is not present on most normal tissues except for nerves. Thus, anti-GD2 antibody treatment causes substantial, dose-limiting neuropathic pain. B7-H3 is overexpressed on multiple tumor types, including neuroblastoma, and is largely absent on nerves and other normal tissues. We designed a bispecific antibody (bsAb) that requires simultaneous binding of these two tumor antigens to achieve tight binding of tumor cells. Our preclinical research shows that, compared with a monospecific anti-GD2 antibody, the GD2xB7-H3 bsAb has improved tumor specificity, comparable antitumor efficacy, and reduced nerve binding and pain-associated toxicity. Since this bsAb does not bind to nerves, it may permit more tolerable and sustained treatment schedules than are currently feasible with monospecific anti-GD2 antibodies. In addition, its enhanced tumor specificity may support future development as a targeted delivery platform for antibody-drug conjugates or other payload-based therapies, potentially improving both efficacy and quality of life for patients with neuroblastoma.

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Erbe, A., Feils, A., Reinthaler, S., Hampton, A., Rosenkrans, Z., Medina Guevara, Y., Felder, M., Wiwczar, J., Gerhardt, D., Bercher, M., Wenke, B., Haertle, C., Heck, M., Heimstreet, K., Frankel, E., Nielsen, M., Spiegelman, D., Tsarovsky, N., Zaborek, J., Rakhmilevich, A., Hank, J., Aluicio-Sarduy, E., Engle, J., Davis, J., Glaser, B., Subbotin, V., Green, R., Hernandez, R., Hammer, B., Sondel, P.. 2026-09-22. Bispecific GD2xB7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma. https://doi.org/10.64898/2026.09.21.753180

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