Potent antitumor effect of T cells armed with anti-GD2 bispecific antibody Journal Article
| Authors: | Nakajima, M.; Guo, H. F.; Hoseini, S. S.; Suzuki, M.; Xu, H.; Cheung, N. K. V. |
| Article Title: | Potent antitumor effect of T cells armed with anti-GD2 bispecific antibody |
| Abstract: | Background: Humanized 3F8-bispecific antibody (hu3F8-BsAb) using the IgG(L)-scFv format (where scFv is single-chain variable fragment), where the anti-CD3 huOKT3 scFv is fused with the carboxyl end of the hu3F8 light chain, has potent antitumor cytotoxicity against GD2(+) tumors. To overcome the insufficient number and function of T cells in cancer patients, they can be rejuvenated and expanded ex vivo before arming with hu3F8-BsAb for adoptive transfer, potentially reducing toxic side effects from direct BsAb administration. Procedure: T cells from normal volunteers were expanded and activated ex vivo using CD3/CD28 beads for 8 days. Activated T cells (ATCs) were harvested and co-incubated with a Good Manufacturing Practice grade hu3F8-BsAb at room temperature for 20 min. These armed ATCs were tested for cytotoxicity in vitro and in vivo against human GD2(+) cell lines and patient-derived xenografts in BALB-Rag2−/−IL-2R-γc-KO mice. Results: Hu3F8-BsAb armed ATCs showed robust antigen-specific tumor cytotoxicity against GD2(+) tumors in vitro. In vivo, T cells armed with hu3F8-BsAb were highly cytotoxic against GD2(+) melanoma and neuroblastoma xenografts in mice, accompanied by T-cell infiltration without significant side effects. Only zeptomole (10−21) quantities of BsAb per T cell was required for maximal antitumor effects. Tumor response was a function of T-cell dose. Conclusion: BsAb armed T cells may have clinical utility as the next generation of cytotherapy combined with recombinant BsAb against human tumors for both adult and pediatrics, if autologous T cells can be activated and expanded ex vivo. © 2021 Wiley Periodicals LLC |
| Keywords: | melanoma; neuroblastoma; gd2; bispecific antibody; armed t cells; cytotherapy |
| Journal Title: | Pediatric Blood and Cancer |
| Volume: | 68 |
| Issue: | 7 |
| ISSN: | 1545-5009 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2021-07-01 |
| Start Page: | e28971 |
| Language: | English |
| DOI: | 10.1002/pbc.28971 |
| PUBMED: | 33844437 |
| PROVIDER: | scopus |
| PMCID: | PMC9347186 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2021 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work