The redirected killing of PD-L1 positive tumor cells by the expanded mucosa-associated invariant T (MAIT) cells is mediated with a bispecific antibody targeting TCR Vα7.2 and PD-L1.

Pan-T cell targeting by CD3-based T cell engagers has brought program-shift treatment and management of blood tumors. However, these modalities have been shown to provoke all types of T cells leading to cytokine storm syndrome, and activate Treg cells. Thus, modulating and potentiating the antitumor responses of a specific T cell subset was encouraged. We initially found that high purity of mucosa-associated invariant T (MAIT) cells could be expanded by the combination of plate-immobilized Vα7.2 mAb (Clone 3C10) and IL2 plus IL15. Then, we generated a novel anti-Vα7.2 TCR bsAb, Vα7.2 x PD-L1, to invoke the anti-tumor potency of these expanded MAIT cells. Furthermore, our data have demonstrated that Vα7.2 x PD-L1 could mediate the cell-to-cell conjunction between MAIT cell and tumor cell line, selectively elicit the activation, cytokine production, degranulation, and cytotoxicity of the expanded MAIT cells in the presence of target cell only. Collectively, this proof-of-concept study provides a new tool to explore the clinical potential of MAIT cells in fighting against PD-L1 positive solid tumors and suggests additional encouragement in designing novel T cell engagers targeting TCR alpha chain specific innate-like T cells subsets, other than pan CD3+ T cells. • We provide a simple protocol for expanding MAIT cells from human PBMCs. • We generate a Vα7.2 TCR-specific bsAb, Vα7.2 X PD-L1 on the Y-body platform. • Vα7.2 X PD-L1 redirects the expanded MAIT cells to kill PD-L1 positive tumor cells of various origins. [ABSTRACT FROM AUTHOR]