T7-EA-ROR1 Conjugate for Melanoma and Mammary Cancer Treatment
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Solution Overview
Problem
Current treatments for malignant melanoma and mammary cancer, such as radiotherapy and chemotherapy, are ineffective in completely curing the diseases and often cause adverse reactions, while existing immunotherapies like TLR7 agonists and ROR1 targeting have limitations in stimulating immune responses.
Innovation Solution
A compound (T7-EA) is synthesized by coupling T7 with ethacrynic acid (EA) and further covalently binding it with ROR1 to create T7-EA-ROR1, which enhances innate and adaptive immunity, improving antitumor effects and immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional treatments (radiotherapy, chemotherapy, surgical treatment) are used for malignant melanoma, then tumor cells can be killed, but the treatments cannot completely cure the disease and cause adverse reactions
Solution Approach 1:
The patent combines T7 (a TLR7 agonist that stimulates innate immunity) with EA (ethacrynic acid, a diuretic with anti-tumor effects but poor immunogenicity) to create compound I (T7-EA). This merging allows the conjugate to simultaneously induce strong immune responses through T7 while maintaining anti-tumor activity through EA, thereby improving cure rate without the severe adverse reactions of traditional treatments
Solution Approach 2:
The patent creates composite molecular structures by covalently binding T7 and EA through amide bond formation. The composite compound I integrates the immunostimulatory properties of T7 with the anti-tumor effects of EA, producing a synergistic effect that overcomes the limitations of either component alone and achieves complete cure without significant adverse reactions
2Reliability
If EA (ethacrynic acid) is used for anti-tumor treatment, then anti-tumor effects are produced, but it cannot stimulate specific anti-tumor cell immune response, making side effects obvious and tumor cells relapse
Solution Approach 1:
The patent merges EA (which provides anti-tumor effects) with T7 (which provides strong immunogenicity as a TLR7 agonist) to form compound I. This combination allows the conjugate to stimulate specific anti-tumor cell immune responses through T7's ability to activate dendritic cells and T cells, while EA continues to exert its anti-tumor effects, preventing tumor cell relapse and reducing side effects
Solution Approach 2:
The patent uses the T7 component as an intermediary that bridges EA and the immune system. T7 acts as a mediator that captures and presents tumor-associated antigens to immune cells, converting EA's non-immunogenic anti-tumor activity into an immunologically active process that stimulates specific anti-tumor immunity and prevents relapse
3Reliability
If ROR1 is used as a target for tumor therapy, then metastasis of tumor cells can be inhibited, but ROR1 has weak immunogenicity and cannot stimulate innate immunity
Solution Approach 1:
The patent combines ROR1 (a target protein that inhibits metastasis when blocked) with T7 (a potent immunostimulant) to create compound II (T7-EA-ROR1). This merging allows the conjugate to simultaneously achieve metastasis inhibition through ROR1 targeting while stimulating strong innate and adaptive immune responses through T7, overcoming the weakness of ROR1's low immunogenicity
Solution Approach 2:
The patent creates a composite molecular structure by covalently attaching ROR1 to the T7-EA conjugate. This composite compound II integrates the anti-metastatic properties of ROR1 with the immunostimulatory capabilities of T7, producing a synergistic therapeutic agent that achieves both metastasis inhibition and robust immune activation
4Reliability
If radiotherapy and chemotherapy are used for mammary cancer, then tumor cells can be killed, but normal cells are also killed and the immune system is seriously destroyed
Solution Approach 1:
The patent merges T7 (which selectively stimulates immune responses) with EA (which has anti-tumor effects) to create compound I that can kill tumor cells through immune-mediated mechanisms. This approach spares normal cells because the immune system is selectively activated against tumor antigens rather than causing non-specific damage as in radiotherapy and chemotherapy
Solution Approach 2:
The patent replaces the mechanical and chemical destruction mechanisms of radiotherapy and chemotherapy with a biological immune-mediated mechanism. Instead of using ionizing radiation or cytotoxic chemicals that indiscriminately damage all rapidly dividing cells, the invention uses T7 to activate the patient's own immune system to specifically recognize and eliminate tumor cells, thereby preserving normal cells and immune function
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The new compounds stimulate immune responses, significantly inhibiting tumor growth and metastasis, demonstrating enhanced antitumor efficacy and immunological adjuvant effects, thereby improving treatment outcomes for melanoma and mammary cancer.
Implementation Method 1
TLR7 (Toll like receptor 7) is one of the Toll like receptors whose ligand is mainly a nucleic acid component of the virus, and it can also identify some synthetic small molecular agonists. A stronger immune response can be triggered when TLR7 is activated.
Data Source
AI summary
Compound I and a compound II as well as preparation methods therefor and use thereof are disclosed. A newly synthesized compound of formula I is capable of stimulating congenital immunity and cellular immunity for tumor resistance while greatly improving the antitumor effect of ethacrynic acid (EA), and thus an integrated synergistic anti-tumor dual-immunity drug design is explored. The immune response mechanism for resisting melanoma of the compound as shown in the formula I is demonstrated. A compound that is as shown in a formula II and is prepared from the compound of formula I and ROR1 by means of covalency markedly slows down the growth of subcutaneously transplanted mammary cancer tumor, such that the immune response mechanism, for treating the mammary cancer, of the compound as shown in the formula II is demonstrated.