Blinatumomab, a bispecific T cell engager (
BiTE) antibody targeting CD19 and CD3ε, can redirect T cells toward CD19-positive
tumor cells and has been approved to treat relapsed/refractory B-cell
acute lymphoblastic leukemia (R/R B-ALL). However, chemotherapeutic regimens can severely reduce T cells' number and cytotoxic function, leading to an inadequate response to
blinatumomab treatment in patients. In addition, it was reported that a substantial portion of R/R B-ALL patients failing
blinatumomab treatment had the extramedullary disease, indicating the poor ability of
blinatumomab in treating extramedullary disease. In this study, we investigated whether the adoptive transfer of ex vivo expanded γ9δ2 T cells could act as the effector of
blinatumomab to enhance
blinatumomab's antitumor activity against B-cell
malignancies in vivo. Repeated infusion of
blinatumomab and human γ9δ2 T cells led to more prolonged survival than that of
blinatumomab or human γ9δ2 T cells alone in the mice xenografted with Raji cells. Furthermore, adoptive transfer of γ9δ2 T cells reduced
tumor mass outside the bone marrow, indicating the potential of γ9δ2 T cells to eradicate the extramedullary disease. Our results suggest that the addition of γ9δ2 T cells to the
blinatumomab treatment regimens could be an effective approach to enhancing
blinatumomab's therapeutic efficacy. The concept of this strategy may also be applied to other
antigen-specific
BiTE therapies for other
malignancies.