CD3 engagement as a new strategy for allogeneic “off-the-shelf” T cell therapy

Gongbo Li*, Kayla M. Reid, Kristen Spitler, Nolan Beatty, Justin Boucher, Marco L. Davila

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Allogeneic “off-the-shelf” (OTS) chimeric antigen receptor T cells (CAR-T cells) hold promise for more accessible CAR-T therapy. Here, we report a novel and simple way to make allogeneic OTS T cells targeting cancer. By engineering T cells with a bispecific T cell engager (BiTE), both TCRαβ and CD3ε expression on the T cell surface are dramatically reduced. BiTE-engineered T (BiTE-T) cells show reduced reaction to TCR stimulation in vitro and have low risk of graft-versus-host disease (GvHD) in vivo. BiTE-T cells down-regulated CD3ε/TCRαβ on bystander T cells by releasing BiTEs. BiTE-T cells produce much fewer cytokines and are comparable to CAR-T cells on anti-cancer efficacy in xenograft mouse models with pre-existing HLA-mismatched T cells. Co-expressing co-stimulatory factors or T cell-promoting cytokines enhanced BiTE-T cells. Our study suggests CD3ε engagement could be a new strategy for allogeneic T cell therapy worthy of further evaluation.

Original languageEnglish (US)
Pages (from-to)887-896
Number of pages10
JournalMolecular Therapy - Oncolytics
Volume24
DOIs
StatePublished - Mar 17 2022
Externally publishedYes

Keywords

  • bi-specific T cell engager
  • chimeric antigen receptor T cell
  • graft versus host disease
  • off-the-shelf

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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