LILRB4-Blocking Antibodies for AML Immune Suppression
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Solution Overview
Problem
Current treatments for acute myeloid leukemia (AML) are ineffective, with no new therapies approved in over 30 years, and existing mouse models and limited understanding of LILRBs and their ligands hinder the development of effective molecular targets for this disease.
Innovation Solution
The development of methods and compositions to modulate LILRB activation through its ligands, using reporter cells to identify modulators of LILRB activation, such as antibodies, and administering these modulators to treat AML by blocking or activating LILRB signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cytotoxic chemotherapy is used to treat AML, then initial response may be achieved, but patients will relapse or succumb to disease within 5 years
Solution Approach 1:
The patent changes the therapeutic parameter from conventional cytotoxic chemotherapy to targeted antibody therapy against LILRB4. The antibody therapy modifies the molecular target parameter, shifting from non-specific cell killing to specific receptor blockade, thereby achieving long-term disease control and improved survival rates.
Solution Approach 2:
The patent introduces LILRB4-blocking antibodies as intermediary substances that mediate the therapeutic effect. These antibodies act as intermediaries between the immune system and tumor cells, blocking the LILRB4 receptor to prevent immune suppression and enable T cell-mediated cytotoxicity against AML cells.
2Loss of information
If mouse models are used to study LILRBs, then basic biological functions can be investigated, but the limited value of mouse models hinders development of effective molecular targets
Solution Approach 1:
The patent creates a functional copy system using reporter cells that express the LILRB4 receptor and a fluorescent reporter gene. These reporter cells serve as simplified copies of the complex biological system, allowing detailed study of LILRB4 function and ligand interaction without the limitations of whole mouse models, thereby accelerating target identification.
Solution Approach 2:
The patent segments the complex LILRB signaling system into isolated components: the LILRB4 receptor, its ligands (ApoE, LFA-1), and downstream signaling pathways. This segmentation enables systematic analysis of each component's function and interaction, facilitating the identification of effective molecular targets for therapy.
3Object-affected harmful factors
If LILRB4 is targeted for therapy, then tumor cell infiltration and immune suppression can be blocked, but the mechanism requires identification and administration of specific modulators
Solution Approach 1:
The patent employs reporter cells that automatically report LILRB4 activation status through fluorescent signal emission. This self-reporting mechanism eliminates the need for complex external detection systems, simplifying the monitoring of therapeutic effect while maintaining the ability to identify and administer specific LILRB4 modulators.
Data Source
AI summary
Provided herein are methods and compositions for the identification of modulators of ApoE-induced LILRB activation. Also provided herein are methods of treating cancer comprising the administration of an inhibitor of ApoE-induced LILRB activation. Also provided are methods of treating autoimmune disease or inhibiting the onset of transplant rejection or treating an inflammatory disorder comprising administering an agonist of ApoE-induced LILRB activation to a subject.