Anti-CD3 × anti-GD2 Bispecific Antibody Redirects T-cell Cytolytic Activity to Neuroblastoma Targets

Overview

Journal Pediatr Blood Cancer

Specialties Hematology
Oncology
Pediatrics

Date 2012 Jun 19

PMID 22707078

Citations 47

Authors

Maxim Yankelevich

Sri Vidya Kondadasula

Archana Thakur

Steven Buck

Nai-Kong V Cheung

Lawrence G Lum

Affiliations

Soon will be listed here.

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.

Citing Articles

GD2-targeting therapy: a comparative analysis of approaches and promising directions.

Philippova J, Shevchenko J, Sennikov S Front Immunol. 2024; 15:1371345.

PMID: 38558810 PMC: 10979305. DOI: 10.3389/fimmu.2024.1371345.

Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells.

Yankelevich M, Thakur A, Modak S, Chu R, Taub J, Martin A J Immunother Cancer. 2024; 12(3).

PMID: 38519053 PMC: 10961524. DOI: 10.1136/jitc-2023-008744.

Targeting GD2-positive Refractory/Resistant Neuroblastoma and Osteosarcoma with Anti- CD3 x Anti-GD2 Bispecific Antibody Armed T cells.

Yankelevich M, Thakur A, Modak S, Chu R, Taub J, Martin A Res Sq. 2023; .

PMID: 37986911 PMC: 10659559. DOI: 10.21203/rs.3.rs-3570311/v1.

Targeting GD2 after allogeneic SCT: effector cell composition defines the optimal use of ch14.18 and the bispecific antibody construct NG-CU (GD2-CD3).

Arendt A, Heubach F, Maier C, Giardino S, Jung G, Kowalewski E Cancer Immunol Immunother. 2023; 72(11):3813-3824.

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F77 antigen is a promising target for adoptive T cell therapy of prostate cancer.

Grover P, Nunez-Cruz S, Leferovich J, Wentz T, Bagchi A, Milone M Biochem Biophys Res Commun. 2023; 680:51-60.

PMID: 37717341 PMC: 10591779. DOI: 10.1016/j.bbrc.2023.09.018.

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