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

Miho Nakajima, Hong fen Guo, Sayed Shahabuddin Hoseini, Maya Suzuki, Hong Xu, Nai Kong V. Cheung

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere28971
JournalPediatric Blood and Cancer
Volume68
Issue number7
DOIs
Publication statusPublished - Jul 2021

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Fingerprint

Dive into the research topics of 'Potent antitumor effect of T cells armed with anti-GD2 bispecific antibody'. Together they form a unique fingerprint.

Cite this