LILRB2 Immune Checkpoint Molecule for Drug Development

Overview of LILRB2

Leukocyte immunoglobulin-like receptor B 2 (LILRB2), also called CD85D, ILT4, LIR2, and MIR10, is made up of a transmembrane domain, four extracellular immunoglobulin domains, and three cytoplasmic immunoglobulin-like motifs (ITIMs).

  • Expression of LILRB2

LILRB2 is expressed on various immune cells, including hematopoietic stem cells, platelets, macrophages, DCs, neutrophils, monocytes, basophils, subsets of T cells, NK cells, and activated CD4+ T cells, as well as endothelial cells, mast cell progenitors, and osteoclasts grown in vitro.

  • LILRB2 ligands

Domain structure of LILRB2. (Deng, et al., 2021)Figure 1. Domain structure of LILRB21.

  • Function of LILRB2

LILRB2 belongs to the family of inhibitory immune checkpoint receptors. LILRB2 is implicated in immunotolerance during pregnancy and transplantation, as well as the induction of DC tolerance. It has immunomodulatory effects by releasing inhibitory signals upon binding to its ligands, which can lead to a dampened immunological response, regulating CD4+ T cells activation and Th2 formation. LILRB2 plays a crucial role in maintaining immune tolerance by downregulating immune responses. It can inhibit the activation and function of immune cells, dampening the immune response to self-antigens and preventing excessive inflammation.

LILRB2 in Cancer

LILRB2 expression has been detected in tumor cells and immune cells within the tumor microenvironment. In certain types of cancer, such as melanoma, ovarian cancer, and leukemia, increased LILRB2 expression is associated with immune evasion, tumor progression, and a poor prognosis. Targeting LILRB2 presents an opportunity to restore anti-tumor immune responses.

LILRB2 Targeting for Cancer Immunotherapy

Modulating LILRB2-mediated immune regulation has gained attention as a potential therapeutic strategy. Blocking or inhibiting LILRB2 could enhance the activation of immune cells and promote anti-tumor immune responses. Several approaches are being explored, including monoclonal antibodies, small molecules, and chimeric antigen receptor (CAR) T cell therapy targeting LILRB2. For instance, in co-culture environments, human macrophages treated with a LILRB2 inhibitor are reprogrammed to boost the activation of autologous T cells.

Combination therapies involving LILRB2 modulation may be necessary for optimal therapeutic efficacy. Combining LILRB2 blockade with other immunotherapies, such as immune checkpoint inhibitors or adoptive cell therapy, could potentially enhance anti-tumor immune responses and improve treatment outcomes. Anti-LILRB2 monotherapy or combination with an anti-PD-1 antibody is being studied in clinical trials. Preliminary clinical data demonstrate that anti-cancer responses are generated when anti-LILRB2 antibodies are combined with anti-PD-1 antibodies.

Services at Creative Biolabs

Creative Biolabs is a renowned immune checkpoint drug research and development company with many years of experience. We commit to providing a variety of high-quality LILRB2 immune checkpoint drug development services, including but not limited to:

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Reference

  1. Deng, Mi et al. "Leukocyte immunoglobulin-like receptor subfamily B: therapeutic targets in cancer." Antibody therapeutics vol. 4,1 16-33. 9 Feb. 2021.

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