Cancer immunotherapy by NC410, a LAIR-2 Fc protein blocking human LAIR-collagen interaction

Collagens are a primary component of the extracellular matrix and functional ligands for inhibitory immune receptor leukocyte-associated immunoglobulin-like (LAIR)-1. LAIR-2 is secreted protein that can act as decoy by binding collagen with higher affinity than LAIR-1. We propose collagens promote evasion interacting LAIR-1 expressed on cells, releases LAIR-1-mediated suppression. Analysis public human datasets shows collagens, have unique overlapping associations survival in certain tumors. designed dimeric IgG1 Fc tail, NC410, showed NC410 increases T cell expansion effector function vivo mouse xenogeneic-graft versus-host disease model. In humanized tumor models, reduces growth dependent cells. Immunohistochemical analysis tumors binds to collagen-rich areas where + cells localized. Our findings show might be novel strategy cancer immunotherapy immune-excluded