IL-15 Conjugate and PD-1 Antibody Combination for Cancer Therapy
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Solution Overview
Problem
Current cancer treatment strategies involving immunosuppressive receptor inhibition or co-stimulatory receptor activation often yield hazardous results and have limited effectiveness in achieving tumor remission, particularly when used alone.
Innovation Solution
A combined pharmaceutical composition comprising a conjugate of interleukin 15 (IL-15) or its derivatives and the sushi domain of IL-15Ra, along with an antibody antagonizing an immune pathway implicated in T cell activation, such as PD-1, is administered to synergistically inhibit tumor growth, allowing for simultaneous, separate, or sequential use in treating cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive receptor inhibition or co-stimulatory receptor activation is used alone, then treatment simplicity is maintained, but tumor remission effectiveness is limited and results are hazardous
Solution Approach 1:
The patent combines an IL-15 superagonist conjugate (comprising IL-15 polypeptide and IL-15Ra sushi domain polypeptide) with an antibody antagonizing an immunosuppressive receptor pathway (such as anti-PD-1 antibody) into a single combined pharmaceutical composition. This merging of two previously separate treatment approaches into one composition achieves synergistic anti-tumor effects while simplifying the treatment regimen for clinical application.
2Reliability
If high-dose monotherapy is administered, then potential therapeutic effect is maximized, but toxicity and hazardous results increase
Solution Approach 1:
The patent employs low doses of both the IL-15 superagonist conjugate and the immunosuppressive receptor antagonist antibody in combination, where each component is administered at a dose lower than what would be required for monotherapy. This partial action approach achieves synergistic therapeutic effects while reducing the toxicity and hazardous results associated with high-dose monotherapy.
3Object-affected harmful factors
If low-dose combination therapy is administered, then treatment safety is improved, but initially tumor remission was not achievable with single agents
Solution Approach 1:
The patent converts the previously harmful or ineffective low-dose approach into a beneficial treatment by combining two low-dose agents that work synergistically. The IL-15 superagonist conjugate and immunosuppressive receptor antagonist, when used together at low doses, achieve tumor remission that neither agent could achieve alone, transforming a potentially ineffective approach into a highly effective therapy.
Data Source
AI summary
The present invention relates to a combined pharmaceutical composition, adapted for simultaneous, separate, or sequential administration for treating cancer in a subject comprising (a) a conjugate comprising (i) a polypeptide comprising the amino acid sequence of interleukin 15 or derivatives thereof, and ii) a polypeptide comprising the amino acid sequence of the sushi domain of IL-15Rα or derivatives thereof; a polynucleotide coding therefore, or a vector comprising such a polynucleotide; and (b) an antibody antagonizing an immune pathway implicated in the inhibition of T cell activation, or a fragment thereof, a polynucleotide coding therefore, or a vector comprising such a polynucleotide.