BTK and ROR-1 Antagonist Combination for CLL Treatment
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Solution Overview
Problem
Current treatments for chronic lymphocytic leukemia (CLL) using BTK inhibitors like ibrutinib show significant clinical activity but face challenges in eradicating the disease and managing relapse, particularly due to residual B-cell signaling pathways.
Innovation Solution
The combination of a Bruton's tyrosine kinase (BTK) antagonist with a tyrosine kinase-like orphan receptor 1 (ROR-1) antagonist, either as a pharmaceutical composition or through administration, is used to treat cancer, specifically targeting and inhibiting BCR signaling pathways in CLL.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If BTK inhibitors like ibrutinib are used to treat CLL, then significant clinical activity and lymph node response are achieved, but eradication of disease and management of relapse remain challenging due to residual B-cell signaling pathways
Solution Approach 1:
The patent segments the B-cell signaling pathway into multiple targets by combining BTK inhibition with ROR-1 inhibition. Instead of relying on a single BTK inhibitor that leaves residual signaling, the treatment divides the signaling pathway into two distinct targets (BTK and ROR-1), each blocked by a different agent, thereby achieving more complete pathway suppression and improving disease eradication efficacy
Solution Approach 2:
The patent employs a composite therapeutic approach by combining two different antagonists (BTK antagonist and ROR-1 antagonist) into a unified treatment regimen. This composite strategy targets multiple nodes within the B-cell receptor signaling network, creating a more robust blockade that prevents residual signaling and reduces relapse risk
2Reliability
If combination therapy with BTK antagonist and ROR-1 antagonist is used, then additive inhibitory effect on CLL cell proliferation is achieved, but treatment complexity increases
Solution Approach 1:
The patent merges two therapeutic agents (BTK antagonist and ROR-1 antagonist) into a single combination regimen that targets complementary nodes in the B-cell signaling pathway. By combining these agents with complementary mechanisms of action, the treatment achieves additive inhibitory effects on CLL cell proliferation while managing the complexity through rational drug pairing
Data Source
AI summary
There are provided, inter alia, compositions and methods for treatment of cancer. The methods include administering to a subject in need a therapeutically effective amount of a Bruton's tyrosine kinase (BTK) antagonist and a ROR-1 antagonist. Further provided are pharmaceutical compositions including a BTK antagonist, ROR-1 antagonist and a pharmaceutically acceptable excipient. In embodiments, the BTK antagonist is ibrutinib and the ROR-1 antagonist is cirmtuzumab.