A recent meta-analysis of expression signatures from ~18,000 human tumors with overall survival outcomes demonstrated that intra-tumoral γδ T-cell signatures constituted the most favorable cancer-wide prognostic cell population across 39 malignancies [1].

Moreover, activation of residing Vγ9Vδ2 T-cells or adoptive transfer of Vγ9Vδ2 T-cells can result in clinically significant tumor responses [2-5].

LAVA’s Vγ9Vδ2 T-cell engagers uniformly and specifically bind to the conserved (monomorphic) T-cell receptor of Vγ9Vδ2 T-cells that constitute a unique proinflammatory immune effector cell population, providing a consistent response and avoid generalized T cell activation known to induce side effects and to reduce anti-tumor effects. The cells exhibit potent cytotoxicity and interferon-γ secretion and HLA-unrestricted tumor cell killing and have antigen-presenting capabilities for αβ-T cells promoting the development of  adaptive immune responses.

Proof of principle has been established by in vitro and in vivo studies in which Vγ9Vδ2 T-cell engagers demonstrate potent tumor lysis independent of signaling escape mechanisms.

The company is working on several lead bispecific Vγ9Vδ2 T-cell engager candidates progressing towards the clinic.