Recombinant Polypeptide Induces Three Pre-Apoptotic DAMPs
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Solution Overview
Problem
Current cancer therapies, such as chemotherapy and radiotherapy, induce immunogenic cell death incompletely by only expressing one or two pre-apoptotic DAMPs, leading to poor anti-tumor immune responses and adverse effects, while there is a need for methods that induce all three pre-apoptotic DAMPs to enhance immunogenic cell death efficiency and minimize side effects.
Innovation Solution
A method involving the administration of a recombinant polypeptide with at least 95% sequence identity to SEQ ID NO: 9, or its encoding nucleic acid, in specific timed doses to reduce IL-10 levels and induce the expression of calreticulin, HSP70, and HSP90, thereby enhancing dendritic cell activation and adaptive immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapy or radiotherapy is used to induce immunogenic cell death, then cell death is achieved, but only one or two pre-apoptotic DAMP signals are induced leading to poor anti-tumor immune responses
Solution Approach 1:
The patent changes the molecular parameter by introducing a recombinant polypeptide with specific amino acid sequence (SEQ ID NO: 9) that has the capability to induce all three pre-apoptotic DAMP signals (CRT, HSP70, HSP90) simultaneously, unlike conventional chemotherapy or radiotherapy that only induce one or two signals. This parameter change in the therapeutic agent's molecular structure enables complete DAMP induction and superior immunogenic cell death.
2Object-affected harmful factors
If chemotherapy or radiotherapy is used to treat cancer, then tumor cells are targeted, but immunosuppressive effects occur reducing lymphocyte numbers and causing collateral damage
Solution Approach 1:
The patent converts the harmful immunosuppressive effect into a beneficial outcome by using the recombinant polypeptide to induce strong immunogenic cell death that activates dendritic cells and promotes anti-tumor immune responses. Instead of suppressing immunity like chemotherapy, the polypeptide enhances immune activation through complete DAMP signal induction (CRT, HSP70, HSP90), transforming the harmful immunosuppressive pathway into a beneficial immunostimulatory effect.
3Quantity of substance
If conventional therapies are used to induce immunogenic cell death, then some DAMP signals are expressed, but not all three pre-apoptotic DAMPs are induced simultaneously
Solution Approach 1:
The recombinant polypeptide with amino acid sequence SEQ ID NO: 9 possesses multi-functionality by simultaneously inducing all three pre-apoptotic DAMP signals (calreticulin, HSP70, and HSP90) in tumor cells. This universal capability distinguishes it from conventional therapies that can only induce one or two signals, making the polypeptide a comprehensive immunogenic cell death inducer that addresses all necessary DAMP pathways.
Data Source
AI summary
The present disclosure provides methods of preventing, delaying the progression of, treating or alleviating a symptom of, or otherwise ameliorating cancer in a subject by administering a recombinant polypeptide and an agent that reduces IL-10 to a subject in need thereof.