Potent antitumor effect of T cells armed with anti-GD2 bispecific antibody.

Autor: Nakajima M; Department of Pediatrics, Memorial Sloan Kettering Cancer Center (MSK), New York, New York, USA.; Department of Pediatric Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan., Guo HF; Department of Pediatrics, Memorial Sloan Kettering Cancer Center (MSK), New York, New York, USA., Hoseini SS; Department of Pediatrics, Memorial Sloan Kettering Cancer Center (MSK), New York, New York, USA., Suzuki M; Department of Pediatrics, Memorial Sloan Kettering Cancer Center (MSK), New York, New York, USA.; Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan., Xu H; Department of Pediatrics, Memorial Sloan Kettering Cancer Center (MSK), New York, New York, USA., Cheung NV; Department of Pediatrics, Memorial Sloan Kettering Cancer Center (MSK), New York, New York, USA.
Jazyk: angličtina
Zdroj: Pediatric blood & cancer [Pediatr Blood Cancer] 2021 Jul; Vol. 68 (7), pp. e28971. Date of Electronic Publication: 2021 Apr 12.
DOI: 10.1002/pbc.28971
Abstrakt: 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.)
Databáze: MEDLINE
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