Bispecific Anti-LILRB4 Antibodies for T-Cell Recruitment in AML
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Solution Overview
Problem
There is a significant need for novel anti-LILRB4 antibodies to target LILRB4, a type I membrane protein that inhibits immune cell activation and supports tumor cell infiltration, particularly in cancers such as acute myeloid leukemia (AML), as existing treatments are inadequate.
Innovation Solution
Development of anti-LILRB4 antibodies and antigen-binding fragments, including bispecific antibodies capable of binding to LILRB4 and CD3, with specific amino acid sequences, and their use in pharmaceutical compositions and chimeric antigen receptors (CAR) for targeted cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used for LILRB4-targeted therapy, then treatment simplicity is maintained, but therapeutic efficacy is insufficient due to inadequate targeting capability
Solution Approach 1:
The patent combines multiple functional capabilities into a single bispecific antibody molecule that can simultaneously bind to LILRB4 on tumor cells and CD3 on T cells, merging targeting and immune activation functions into one therapeutic agent to improve efficacy without requiring combination therapy
Solution Approach 2:
The bispecific antibody performs multiple functions: it targets LILRB4-expressing tumor cells, recruits and activates T cells through CD3 binding, and blocks the immunosuppressive LILRB4 signaling pathway, providing multi-functional therapeutic action against drug-resistant AML
2Object-affected harmful factors
If LILRB4 is left untargeted, then immune system operates normally, but tumor cell infiltration is supported and T cell activation is suppressed
Solution Approach 1:
The patent converts the harmful immunosuppressive function of LILRB4 into a therapeutic target by designing an antibody that specifically binds to LILRB4, blocking its ability to suppress T cell activation and promote tumor infiltration, thereby transforming the pathological mechanism into a treatment avenue for drug-resistant AML
3Manufacturing precision
If conventional antibodies are used, then manufacturing simplicity is maintained, but binding specificity and affinity to LILRB4 are insufficient
Solution Approach 1:
The patent applies local quality by designing specific complementarity-determining regions (CDRs) with optimized amino acid sequences that confer high binding specificity to LILRB4, while using humanized framework regions to maintain manufacturability and reduce immunogenicity, achieving both specificity and production feasibility
Data Source
AI summary
The present disclosure provides anti-LILRB4 antibodies or antigen-binding fragments thereof, anti-LILRB4 chimeric antigen receptor protein, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and the uses thereof.