LILRB1 expression on myeloid cells regulates both innate and adaptive immune responses. Researchers at UTHealth Houston and UTSW developed novel agonistic anti-LILRB1 monoclonal antibodies (mAbs) for autoimmune and inflammatory disease treatments, and novel antagonistic anti-LILRB1 mAbs for cancer immunotherapies.
Background
LILRB1, a member of the ITIM-containing LILR receptor family, plays critical roles in regulation of both innate and adaptive immunity. It is expressed on several types of immune cells, including NK cells, and acts as an immune checkpoint protein. LILRB1 expression in myeloid-derived suppressor cells (MDSCs) can promote tumor growth and result in a suppressive immune microenvironment for tumor progression and metastasis. Study shows that the percentage of LILRB1-expressing NK cells is significantly higher in patients with late-stage cancer or poor prognosis, and thus LILRB1 may be a molecular target for immunotherapy for these patients. On the other hand, activation of LILRB1 signaling using agonistic antibodies can reduce tissue inflammation and can be used for management of autoimmune diseases. Therefore, both agonistic and antagonistic human anti-LILRB1 mAbs have potentials to treatment different human diseases, including cancers and auto-immune diseases.
Significance and Impact
Researchers at UTHealth Houston and The University of Texas Southwestern Medical Center (UTSW) identified that the percentage of LILRB1-expressing NK cells is significantly higher in patients with late-stage cancer or poor prognosis, and thus LILRB1 may be a molecular target for immunotherapy for these patients. They further developed both agonistic and antagonistic humanized anti-LILRB1 mAbs. They also demonstrated LILRB1 blockade via antagonistic anti-LILRB1 mAbs increased the tumoricidal activity of NK cells against several types of cancer cells, including multiple myeloma, leukemia, lymphoma and solid tumors, in vitro and in vivo.
Benefits/Technology Advantages
Related Publications
Heyu Chen et al. J. Immunother. Cancer. 2020. doi: 10.1136/jitc-2019-000515.