LILRB4 Immune Checkpoint Molecule for Drug Development

Overview of LILRB4

The constituents of the human leukocyte immunoglobulin-like receptor (LILR) cohort are found to express on leukocytes and frequently exhibit perturbations across a spectrum of pathogenic conditions. Within this assemblage, 5 members (LILRA1, 2, 4-6) function as activators, another set of 5 (LILRB1-5) as inhibitors, and a solitary entity (LILRA3) manifest in a soluble form, collectively orchestrating the modulation of immune reactions. Their architectural configuration encompasses either 2 or 4 analogous C-2-type Ig-like extracellular domains, while divergences emerge within their transmembrane and intracellular segments.

LILRB4 is a representative of inhibitory LILRs, which are characterized by the presence of a mere pair of extracellular Ig-like domains. Diverse cellular subsets, encompassing myeloid lineages, precursor mast cells, and osteoclasts, demonstrate the expression of LILRB4. In the realm of oncological investigations, 2 ligands for LILRB4 have been recently unveiled: apolipoprotein E and CD166-triggered leukocyte cell adhesion molecule.

Fig. 1 Configuration, cellular dispersion, and ligands of the LILRs.¹

LILRB4 as a Hot Immune Checkpoint and Signal Pathway

The myeloid inhibitory receptor LILRB4 (alternatively known as ILT3, LIR-5, CD85k), an integral component within the leukocyte immunoglobulin-like receptor (LILRs/LIRs) family, assumes a pivotal role in the orchestration of immune tolerance, encompassing diverse functionalities:

In homeostasis:
LILRB4 stimulates the immune functionalities of monocytes, provokes macrophage stimulation through the attenuation of FcgR signaling, reduces the stimulation and maturation of CD4⁺ Th cells, or instigates the formation of CD8⁺ T suppressive cells within tolerogenic dendritic cells (tDCs);
In inflammation disorders
LILRB4 exhibits immunosuppressive roles in MDSCs and TAMs by governing the synthesis of cytokines that foster immune inhibition;
In tumors:
LILRB4 fosters infiltration of leukemia cells and elicits T cell suppression within acute myeloid leukemia (AML) via engagement with the NF-κB signaling cascade.

Fig. 2 LILRB4's functional repertoire.²

Case Study

Construction and characterization of homogeneous anti-LILRB4 ADCs. (Anami, et al., 2020)

Fig. 3 Construction and characterization of homogeneous anti-LILRB4 ADCs.³
Antibody-drug conjugates (ADCs) present a propitious pharmacotherapeutic avenue for the treatment of acute myeloid leukemia (AML). This article has illuminated LILRB4 as a prospective ADC target for eradicating monocytic AML cells while preserving the viability of their healthy counterparts.

Specific binding of primary human t cells transduced with anti-LILRB4 CAR to the target LILRB4 protein. (John, et al., 2018)

Fig. 4 Specific binding of primary human t cells transduced with anti-LILRB4 CAR to the target LILRB4 protein.⁴
Chimeric antigen receptor (CAR)-engineered T cells directed towards antigens linked with tumors have exhibited encouraging results in addressing certain malignancies. This study has yielded a groundbreaking anti-LILRB4 CAR-T cell variant, demonstrating elevated antigen affinity and selectivity. In vitro and in vivo assessments underscore the robust effector capability of these CAR-T cells against AML cells marked by LILRB4 expression.

Services

Creative Biolabs contributes substantial acumen in drug exploration and advancement to address this endeavor, synergistically aligning with more than ten years of scholarly collaboration, in order to scrutinize the involvement of this receptor family in cancer. Our prominently featured services pertain to immune checkpoint assays, the development of immune checkpoint antibodies, etc.

Creative Biolabs has developed comprehensive services to checkpoint molecular LILRB4, which emerges as a compelling therapeutic focal point, regulating immune dynamics in the etiology of diverse disorders prominently including malignancies. If you want to get more details, please contact us to inform us of your requirements.

References

Abdallah, Florence, et al. "Leukocyte immunoglobulin-like receptors in regulating the immune response in infectious diseases: A window of opportunity to pathogen persistence and a sound target in therapeutics." Frontiers in Immunology 12 (2021): 717998.
Yang, Ting, et al. "LILRB4, an immune checkpoint on myeloid cells." Blood Science 4.02 (2022): 49-56.
Anami, Yasuaki, et al. "LILRB4-targeting antibody–drug conjugates for the treatment of acute myeloid leukemia." Molecular cancer therapeutics 19.11 (2020): 2330-2339.
John, Samuel, et al. "A novel anti-LILRB4 CAR-T cell for the treatment of monocytic AML." Molecular Therapy 26.10 (2018): 2487-2495.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.