Study Provides First Preclinical Evidence of a Bispecific Trifunctional Antibody–Induced Anti-Tumor Vaccination Effect in Neuroblastoma

A research team in Berlin has published what they say is the first evidence that a disialoganglioside 2–directed bispecific trifunctional antibody (trAb) – a molecule engineered to have two antigen-binding sites, enabling it to simultaneously bind to a tumor-associated antigen and a T-cell receptor (TCR) complex CD3 – can mediate TCR–independent T-cell anti-tumor responses and induce an anti-tumor vaccination effect that prolonged survival in a tumor-challenged murine model of neuroblastoma.

The study shows for the first time that the SUREK trAb “induces a tumor-specific immunological memory, which was completely absent after tumor vaccination alone,” write Felix Zirngibl, MD, and colleagues at the Berlin Institute of Health. “The production of tumor-directed antibodies was increased by a combination therapy with anti-Pd-1 checkpoint inhibition.” The study appears in the January issue of Frontiers in Immunology.

Novel therapies are needed for neuroblastoma, the most common extracranial solid tumor in children with overall survival in recurrent disease that ranges from 2% to 15%, the authors write. “Combining tumor vaccination and SUREK trAb treatment with additional checkpoint inhibitors might further improve anti-tumor effector function and could translate into the clinic as a prophylactic therapy option for children with minimal residual disease.”

Reference

Ivasko SM, Anders K, Grunewald L, et al. Combination of GD2-directed bispecific trifunctional antibody therapy with Pd-1 immune checkpoint blockade induces anti-neuroblastoma immunity in a syngeneic mouse model. Front Immunol. 2023;13:1023206. Published Jan 9, 2023. doi:10.3389/fimmu.2022.1023206