versikine

Versikine is a bioactive matrikine derived from the N-terminal proteolysis of the large extracellular matrix proteoglycan versican (VCAN). It functions as an endogenous immunomodulatory signaling molecule that bridges innate and adaptive immunity within the tumor microenvironment. Versikine primarily signals through Toll-like receptor 2 (TLR2) on dendritic cells (DCs), particularly the Batf3-lineage, to induce the production of cytokines such as IL-12 and promote the recruitment of T follicular helper (Tfh)-like CD4+ T cells. This process facilitates the formation of "immune triads" consisting of DCs, CD4+ T cells, and CD8+ effector T cells, thereby enhancing T-cell infiltration and cytolytic activity in otherwise immune-excluded or "cold" tumors. Versikine is being developed as a therapeutic agent, delivered either as a recombinant protein or via lipid nanoparticle (LNP)-encapsulated mRNA, to overcome resistance to checkpoint inhibition immunotherapy in patients with low endogenous versican proteolysis.

Other names

VCAN-derived matrikineversican fragmentVCAN fragment