Radioprotectants Targeting TSP-1 and CD47 Interaction
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Solution Overview
Problem
Current radiation therapies cause significant adverse effects on non-target tissues, leading to morbidity and limiting the therapeutic efficacy of cancer treatments due to the lack of effective radioprotectants that can inhibit radiation-induced damage without affecting tumor ablation.
Innovation Solution
Inhibiting the interaction between thrombospondin-1 (TSP-1) and CD47 using antisense molecules, peptides, and antibodies to protect non-target tissues from radiation damage, while enhancing tumor ablation during radiotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If radiation dose is increased to enhance tumor ablation, then tumor treatment efficacy is improved, but tissue damage to non-target tissues increases
Solution Approach 1:
The patent introduces TSP-1 and CD47 as intermediary targets to mediate the selective effect of radiation. By inhibiting the TSP-1/CD47 interaction in non-target tissues, the patent creates a molecular mediator that differentiates between protected and affected tissues, allowing high radiation doses to be administered without damaging normal tissues while enhancing tumor ablation
Solution Approach 2:
The patent applies local quality by creating differential protection at the molecular level. Through selective inhibition of TSP-1/CD47 interaction in non-target tissues, the patent endows different tissues with different radiation sensitivities, allowing normal tissues to be protected while tumors remain vulnerable to radiation-induced ablation
2Object-affected harmful factors
If radioprotectants are used to protect non-target tissues, then tissue damage is reduced, but tumor ablation efficacy may be compromised
Solution Approach 1:
The patent inverts the conventional approach by not directly protecting tissues from radiation damage, but rather by modulating the TSP-1/CD47 interaction to create selective vulnerability. Instead of shielding normal tissues, the patent enhances radiation-induced tumor ablation while normal tissues are protected through the molecular interaction inhibition, effectively inverting the traditional protectant mechanism
3Reliability
If TSP-1/CD47 interaction is inhibited, then non-target tissue survival is improved, but the mechanism of action requires complex molecular targeting
Solution Approach 1:
The patent changes the molecular parameter of the TSP-1/CD47 interaction by introducing inhibitors that alter the binding affinity or interaction dynamics between these proteins. This parameter change at the molecular level translates to macroscopic tissue protection, simplifying the complex molecular targeting into a manageable therapeutic intervention through small molecules or antibodies
Data Source
Figure 1A~1E
Figure 2A~3
Figure 4~5B
AI summary
Described herein is the discovery that cell and tissue survival can be dramatically increased following radiation exposure through inhibition of the interaction between TSP-1 and CD47. This effect is shown using antisense molecules, peptides, and antibodies, which can now be used as radioprotectant agents. These agents find application in minimizing, reducing and/or preventing tissue damage following intentional and accidental radiation exposure, as well as increasing the therapeutic efficacy of radiation therapies by protecting non-target tissue from incidental radiation damage and by increasing tumor ablation following radiation treatment.