Authors
Amy K Erbe, Arika S Feils, Sabrina N Reinthaler, Alina Hampton, Zachary T Rosenkrans, Yadira Guevara, Mildred Felder, Jessica Wiwczar, Daniel J Gerhardt, Mark Bercher, Belinda Wenke, Callie Haertle, Mackenzie Heck, Kaia Heimstreet, Elizabeth Frankel, Megan Nielsen, Dan Spiegelman, Noah Tsarovsky, Jen Zaborek, Alexander L Rakhmilevich, Jacquelyn A Hank, Eduardo Aluicio-Sarduy, Jonathan W Englev, Jonathan H Davis, Bryan Glaser, Vladimir Subbotin, Roland Green, Reinier Hernandez, Bonnie Hammer, Paul M Sondel
Published in
bioRxiv : the preprint server for biology. Sep 22, 2026. Epub Sep 22, 2026.
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 GD2×B7-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.
PMID:
42818194
Bibliographic data and abstract were imported from PubMed on 01 Oct 2026.
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