Bispecific GD2 x B7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma

Abstract

The current treatment for neuroblastoma involves an immunotherapy regimen that includes a monoclonal antibody that recognizes disialoganglioside (GD2), expressed at high levels on neuroblastoma. GD2 is not present on most normal tissues but is expressed on nerves. Thus, anti-GD2 treatment causes substantial, dose-limiting, neuropathic pain. B7-H3 is overexpressed on multiple tumor types, including neuroblastoma, with minimal normal cell expression and is absent on nerves. 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 when compared to an anti-GD2 monospecific antibody, the GD2xB7-H3 bsAb has improved tumor specificity with similar efficacy and reduced toxicity. Since this bsAb does not bind to nerves, it may be possible to administer increased or additional doses beyond the tolerable dose of monospecific anti-GD2 antibodies, which could improve therapeutic efficacy and quality of life for patients with neuroblastoma.

Targeting both GD2 and B7-H3 using bispecific antibody improves tumor selectivity for GD2-positive tumors

“…Additional validation of our findings that bispecific antibodies improve antibody selectivity should be extended to other tumors expressing GD2 and B7-H3. Analyses addressing these issues are beyond the scope of this manuscript, but several of these questions are addressed in a separate manuscript evaluating a novel anti-GD2/anti-B7-H3 bispecific antibody [35]. Following the necessary preclinical studies, the next generation GD2/B7-H3 bispecific antibody holds promise to supersede existing anti-GD2 antibody therapies for cancer patients, ultimately improving treatment quality.…”