Leukocyte associated immunoglobulin like receptor 1 (LAIR1 or CD305) is an immune inhibitory receptor expressing on most immune cell types. Researchers at UTHealth Houston and UTSW generated novel antagonistic anti-LAIR1 monoclonal antibodies (mAbs) that inhibited the activity of immunosuppressive myeloid cells and reactivated T cells from cancer patients in vitro and impeded tumor metastasis in a humanized mouse model.
Background
As an immune inhibitory receptor, LAIR1 was reported to have the function on regulating immune system balance and protecting tissue damages against a hyperactive immune response or autoimmune dysfunction. Previous studies showed that LAIR1 deficiency retards development of acute myeloid leukemia (AML) and Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ B-ALL). In chronic lymphoblastic leukemia (CLL), down-regulation of LAIR1 correlates with increased risk of disease. As for solid tumors, although LAIR1 was found abnormally upregulated on certain solid cancer cells, its main function during solid cancer development may result from its inhibition of activation of multiple types of immune cells.
Significance and Impact
Researchers at UTHealth Houston and The University of Texas Southwestern Medical Center (UTSW) developed novel anti-LAIR1 mAbs. The antagonistic anti-LAIR1 mAbs stimulated the activities of T cells, natural killer cells, macrophages, and dendritic cells in vitro. Importantly, treatment with antagonistic anti-LAIR1 mAbs significantly inhibited the activity of immunosuppressive myeloid cells and re-stimulated T cell proliferation from cancer patients in vitro and impeded tumor metastasis in humanized mice. These results suggest that blocking LAIR1 signaling with antagonist antibodies represents a new attractive anti-cancer strategy. In addition, our researchers also generated agonist anti-LAIR1 mAbs that inhibits T cell activities and potentially for autoimmune disease treatment.
Benefits/Technology Advantages
Related Publications
Xie, Jingjing, et al. "Blocking LAIR1 signaling in immune cells inhibits tumor development." Frontiers in immunology 13 (2022): 996026.