Cutting Edge: Bispecific γδ T Cell Engager Containing Heterodimeric BTN2A1 and BTN3A1 Promotes Targeted Activation of Vγ9Vδ2⁺ T Cells in the Presence of Costimulation by CD28 or NKG2D.

ABSTRACT: Vγ9Vδ2⁺ T cell-targeted immunotherapy is of interest to harness its MHC-independent cytotoxic potential against a variety of cancers. Recent studies have identified heterodimeric butyrophilin (BTN) 2A1 and BTN3A1 as the molecular entity providing "signal 1" to the Vγ9Vδ2 TCR, but "signal 2" costimulatory requirements remain unclear. Using a tumor cell-free assay, we demonstrated that a BTN2A1/3A1 heterodimeric fusion protein activated human Vγ9Vδ2⁺ T cells, but only in the presence of costimulatory signal via CD28 or NK group 2 member D. Nonetheless, addition of a bispecific γδ T cell engager BTN2A1/3A1-Fc-CD19scFv alone enhanced granzyme B-mediated killing of human CD19⁺ lymphoma cells when cocultured with Vγ9Vδ2⁺ T cells, suggesting expression

SUBMITTER: Lai AY 

PROVIDER: S-EPMC9527206 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature