Anti-CD3 × anti-GD2 bispecific antibody redirects T-cell cytolytic activity to neuroblastoma targets. Academic Article uri icon

Overview

abstract

  • BACKGROUND: The ganglioside GD2 is an attractive target for immunotherapy of neuroectodermal tumors. We tested a unique bispecific antibody anti-CD3 × anti-GD2 (3F8BiAb) for its ability to redirect activated T cells (ATC) to target GD2-positive neuroblastomas. PROCEDURE: ATC were generated from normal human peripheral blood mononuclear cells (PBMC) by stimulating the PBMC with OKT3 and expanding the T cells in the presence of interleukin 2 (IL-2) for 14 days. ATC were armed with 3F8BiAb (100 ng/10(6) cells) or Her2BiAb (50 ng/10(6) cells) prior to use. 3F8 BiAb were tested for its dual-binding specificity to GD2 expressed on cancer cell lines and CD3 expressed on ATC. 3F8BiAb-armed ATC were further tested ex vivo for their cytotoxicity against GD2 positive tumor targets and its ability to induce cytokine response upon binding to targets. RESULTS: GD2 expression in neuroblastoma cells was confirmed by FACS analysis. Specific binding of 3F8BiAb to the tumor targets as well as to ATC was confirmed by FACS analysis. 3F8BiAb-armed ATC exhibited specific killing of GD2 positive neuroblastoma cell lines significantly above unarmed ATC (P < 0.001). GD2BiAb-armed ATC secreted significantly higher levels of Th(1) cytokines and chemokines compared to unarmed ATC (P < 0.001). CONCLUSIONS: These preclinical findings support the potential of a novel immunotherapeutic approach to target T cells to neuroblastoma.

publication date

  • June 15, 2012

Research

keywords

  • Antibodies, Bispecific
  • CD3 Complex
  • Gangliosides
  • Neuroblastoma
  • T-Lymphocytes, Cytotoxic

Identity

PubMed Central ID

  • PMC3792711

Scopus Document Identifier

  • 84867375009

Digital Object Identifier (DOI)

  • 10.1002/pbc.24237

PubMed ID

  • 22707078

Additional Document Info

volume

  • 59

issue

  • 7