학술논문
Cancer immunotherapy by NC410, a LAIR-2 Fc protein blocking human LAIR- collagen interaction.
Document Type
Article
Author
Pascoal Ramos, M. Ines; Tian, Linjie; de Ruiter, Emma J.; Song, Chang; Paucarmayta, Ana; Singh, Akashdip; Elshof, Eline; Vijver, Saskia V.; Shaik, Jahangheer; Bosiacki, Jason; Cusumano, Zachary; Jensen, Christina; Willumsen, Nicholas; Karsdal, Morten A.; Liu, Linda; Langermann, Sol; Willems, Stefan; Flies, Dallas; Meyaard, Linde
Source
Subject
*IMMUNOTHERAPY
*IMMUNOHISTOCHEMISTRY
*T cells
*LABORATORY mice
*IMMUNOSUPPRESSION
*EXTRACELLULAR matrix
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Language
ISSN
2050-084X
Abstract
Collagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte-associated immunoglobulin-like receptor (LAIR)-1. 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 expressed on immune cells, and that LAIR-2 releases LAIR-1-mediated immune suppression. Analysis of public human datasets shows that collagens, LAIR-1 and LAIR-2 have unique and overlapping associations with survival in certain tumors. We designed a dimeric LAIR-2 with a functional IgG1 Fc tail, NC410, and showed that NC410 increases human T cell expansion and effector function in vivo in a mouse xenogeneic-graft versus-host disease model. In humanized mouse tumor models, NC410 reduces tumor growth that is dependent on T cells. 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 novel strategy for cancer immunotherapy for immune-excluded tumors. [ABSTRACT FROM AUTHOR]