AI Article Synopsis

  • A new treatment, hu3F8-bispecific antibody (hu3F8-BsAb), combines an anti-CD3 component with a cancer-targeting antibody to enhance T cell cancer fighting ability against GD2(+) tumors.
  • T cells from healthy volunteers were activated and expanded outside the body, then combined with hu3F8-BsAb before testing their effectiveness against tumors in lab settings and mouse models.
  • Results showed that these enhanced T cells were highly effective at attacking GD2(+) tumors with minimal side effects, suggesting potential for future cancer therapies in both adults and children.

Article 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 ) 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347186PMC
http://dx.doi.org/10.1002/pbc.28971DOI Listing

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