Anti-CD3×anti-GD2 bispecific antibody redirects T-cell cytolytic activity to neuroblastoma targets Journal Article
| Authors: | Yankelevich, M.; Kondadasula, S. V.; Thakur, A.; Buck, S.; Cheung, N. K. V.; Lum, L. G. |
| Article Title: | 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 (100ng/10 6cells) or Her2BiAb (50ng/10 6cells) 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. © 2012 Wiley Periodicals, Inc. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; t cells; antigens, cd3; interleukin 2; cancer cell culture; cell line, tumor; lymphocyte activation; cytokines; immunotherapy; neuroblastoma; ganglioside gd2; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; receptor, erbb-2; ex vivo study; antibody; peripheral blood mononuclear cell; binding sites, antibody; gangliosides; cytotoxicity tests, immunologic; cd3 antibody; antibodies, bispecific; bispecific antibody; gd-2; cytokine response; gd2 antibody; okt 3 |
| Journal Title: | Pediatric Blood and Cancer |
| Volume: | 59 |
| Issue: | 7 |
| ISSN: | 1545-5009 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2012-12-15 |
| Start Page: | 1198 |
| End Page: | 1205 |
| Language: | English |
| DOI: | 10.1002/pbc.24237 |
| PROVIDER: | scopus |
| PUBMED: | 22707078 |
| PMCID: | PMC3792711 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 November 2012" - "CODEN: PBCEA" - "Source: Scopus" |
