Abstract | BACKGROUND: 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.
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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)
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Copyright | Copyright © 2012 Wiley Periodicals, Inc. |
Chemical References |
- Antibodies, Bispecific
- CD3 Complex
- Cytokines
- Gangliosides
- ganglioside, GD2
- Receptor, ErbB-2
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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)
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