IL-2 Analog Combination Therapy for Anti-Tumor Efficacy With Lower Toxicity
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Solution Overview
Problem
Existing cancer treatments using interleukin-2 and immune checkpoint inhibitors face severe toxicity and limited efficacy, necessitating the development of safer and more effective therapeutics that can activate the immune system to combat cancer.
Innovation Solution
A combination therapy involving an interleukin-2 analog or long-acting conjugate thereof, administered in conjunction with an immune checkpoint inhibitor, to enhance tumor suppression and reduce side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high-dose interleukin-2 therapy is used to treat cancer, then anti-cancer efficacy is improved, but severe toxicity increases
Solution Approach 1:
The patent modifies the amino acid sequence of interleukin-2 to create analogs with altered properties. Specifically, mutations at positions 1, 2, and 128 change the binding affinity to IL-2Rα and IL-2Rβ receptors, reducing immunosuppressive effects while maintaining anti-tumor activity. This parameter change in molecular structure resolves the contradiction by decoupling efficacy from toxicity.
Solution Approach 2:
The patent creates chimeric proteins by combining portions of interleukin-2 with portions of interleukin-15. This composite structure (e.g., IL-2(1-96)-IL-15(97-186) or IL-2(1-101)-IL-15(102-186)) leverages the anti-tumor properties of IL-2 while incorporating the reduced toxicity profile of IL-15, thereby resolving the efficacy-toxicity contradiction.
2Reliability
If immune system is activated to combat cancer, then anti-cancer effects are improved, but side effects due to immune cell overactivity increase
Solution Approach 1:
The patent engineering interleukin-2 analogs with non-uniform receptor binding properties. The mutations create asymmetric binding characteristics where the analog preferentially activates certain immune cell populations (CD8+ T cells and NK cells via IL-2Rβ) while having reduced activity on others (regulatory T cells via IL-2Rα). This local differentiation in immune cell activation resolves the contradiction by targeting cancer-fighting cells while sparing overactive immune responses.
Data Source
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AI summary
The present invention relates to a combined use of an interleukin-2 analog or conjugate thereof and an immune checkpoint inhibitor for preventing or treating cancer and a pharmaceutical composition comprising the same.