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

Ramos, M. I. P.; Tian, L.; de Ruiter, E. J.; Song, C.; Paucarmayta, A.; Singh, A.; Elshof, E.; Vijver, S. V.; Shaik, J.; Bosiacki, J.; Cusumano, Z.; Liu, L.; Langermann, S.; Willems, S.; Flies, D.; Meyaard, L.

doi:10.1101/2020.10.21.349480

bioRxiv · 10.1101/2020.10.21.349480

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

Ramos, M. I. P.·Tian, L.·de Ruiter, E. J.·Song, C.·Paucarmayta, A.·Singh, A.·Elshof, E.·Vijver, S. V.·Shaik, J.·Bosiacki, J.·Cusumano, Z.·Liu, L.·Langermann, S.·Willems, S.·Flies, D.·Meyaard, L.

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Abstract

Collagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte associated immunoglobulin-like receptor-1 (LAIR-1). Leukocyte associated immunoglobulin-like receptor-2 (LAIR-2) is a secreted protein that can act as a decoy receptor by binding collagen with higher affinity than LAIR-1. We propose that collagens promote immune evasion by interacting with LAIR-1 and that LAIR-2 could release LAIR-1 mediated immune suppression. Analysis of public datasets shows high LAIR-2 expression being associated with a favorable outcome in certain tumors. We designed a dimeric LAIR-2 with a functional IgG1 Fc tail, NC410, and showed that NC410 reduces tumor growth and increases T cell expansion and effector function in humanized tumor models. Immunohistochemical analysis of human tumors shows that NC410 binds to collagen-rich areas where LAIR-1+ immune cells are localized. Our findings show that NC410 might be a powerful new strategy for cancer immunotherapy for immune-excluded tumors.

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Ramos, M. I. P., Tian, L., de Ruiter, E. J., Song, C., Paucarmayta, A., Singh, A., Elshof, E., Vijver, S. V., Shaik, J., Bosiacki, J., Cusumano, Z., Liu, L., Langermann, S., Willems, S., Flies, D., Meyaard, L.. 2020-10-22. Cancer immunotherapy by NC410, a LAIR-2 Fc protein blocking LAIR-collagen interaction. https://doi.org/10.1101/2020.10.21.349480

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