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

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.

• Authors: Maxim Yankelevich, Sri Vidya Kondadasula, Archana Thakur, Steven Buck, Nai-Kong V Cheung, Lawrence G Lum
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 59 Issue 7 Pg. 1198-205 (Dec 15 2012) ISSN: 1545-5017 [Electronic] United States
• PMID: 22707078 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Antibodies, Bispecific
• CD3 Complex
• Cytokines
• Gangliosides
• ganglioside, GD2
• Receptor, ErbB-2

Topics

• Antibodies, Bispecific (immunology, therapeutic use)
• Binding Sites, Antibody
• CD3 Complex (immunology)
• Cell Line, Tumor
• Cytokines (metabolism)
• Cytotoxicity Tests, Immunologic
• Gangliosides (immunology, metabolism)
• Humans
• Immunotherapy
• Lymphocyte Activation
• Neuroblastoma (immunology, metabolism, therapy)
• Receptor, ErbB-2 (immunology, metabolism)
• T-Lymphocytes, Cytotoxic (immunology)