Bispecific GD2xB7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma
- 1University of Wisconsin-Madison
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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BibTeX
@misc{erbe2026bispecific,
title = {{Bispecific GD2xB7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma}},
author = {A. Erbe and A. Feils and S. Reinthaler and A. Hampton and Z. Rosenkrans and Y. Medina Guevara and M. Felder and J. Wiwczar and D. Gerhardt and M. Bercher and B. Wenke and C. Haertle and M. Heck and K. Heimstreet and E. Frankel and M. Nielsen and D. Spiegelman and N. Tsarovsky and J. Zaborek and A. Rakhmilevich and J. Hank and E. Aluicio-Sarduy and J. Engle and J. Davis and B. Glaser and V. Subbotin and R. Green and R. Hernandez and B. Hammer and P. Sondel},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753180},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753180v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Bispecific GD2xB7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma
AU - A. Erbe
AU - A. Feils
AU - S. Reinthaler
AU - A. Hampton
AU - Z. Rosenkrans
AU - Y. Medina Guevara
AU - M. Felder
AU - J. Wiwczar
AU - D. Gerhardt
AU - M. Bercher
AU - B. Wenke
AU - C. Haertle
AU - M. Heck
AU - K. Heimstreet
AU - E. Frankel
AU - M. Nielsen
AU - D. Spiegelman
AU - N. Tsarovsky
AU - J. Zaborek
AU - A. Rakhmilevich
AU - J. Hank
AU - E. Aluicio-Sarduy
AU - J. Engle
AU - J. Davis
AU - B. Glaser
AU - V. Subbotin
AU - R. Green
AU - R. Hernandez
AU - B. Hammer
AU - P. Sondel
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.753180
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.753180v1
AB - 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.
ER -