Recombinant Polypeptides for Triple-DAMP Immunogenic Cell Death
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Solution Overview
Problem
Existing cancer therapies like chemotherapy and radiotherapy induce immunogenic cell death with limited efficiency by not expressing all three pre-apoptotic DAMP signals, leading to poor anti-tumor immune responses and adverse effects.
Innovation Solution
Recombinant polypeptides, such as those derived from alpha-crystallin proteins, are engineered to induce the expression of all three pre-apoptotic DAMPs (calreticulin, HSP70, and HSP90) on cancer cells, enhancing immunogenic cell death and activating dendritic cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapy and radiotherapy are used to induce immunogenic cell death, then cell death is achieved, but the expression of all three pre-apoptotic DAMP signals is not induced and immune suppression occurs
Solution Approach 1:
The patent modifies the chemical parameters of the therapeutic agent by combining a platinum-based compound with specific antioxidants (N-acetylcysteine, vitamin C, or vitamin E) at defined molar ratios. This parameter change enables simultaneous induction of all three DAMP signals (CRT, HSP70, HSP90) while reducing immune suppression and collateral damage to non-tumor cells, achieving reliable immunogenic cell death with minimized harmful effects.
2Quantity of substance
If traditional apoptosis is induced in cancer cells, then cell death occurs, but immunogenic response is not activated
Solution Approach 1:
The patent changes the mode of cell death from traditional apoptosis to immunogenic cell death by modifying the therapeutic parameters. The combination of platinum-based compounds with antioxidants at specific molar ratios triggers pre-apoptotic DAMP expression (CRT, HSP70, HSP90), transforming the cell death process to activate dendritic cells and generate effective anti-tumor immune responses while maintaining cancer cell killing.
Data Source
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AI summary
The present disclosure provides recombinant polypeptides, nucleic acids encoding the recombinant polypeptides and methods for using these polypeptides and/or nucleic acids in enhancing or inducing an immune response in a subject in need thereof. The present disclosure also provides methods of treating a cell proliferative disorder, such as cancer, by administering the disclosed polypeptides and/or nucleic acids to a subject in need thereof.