Mutated Oncolytic Virus Combinations for Safer Tumor Cell Killing
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Solution Overview
Problem
Oncolytic viruses face challenges such as pathogenicity and drug resistance, while small-molecule anticancer drugs face inefficiency and drug resistance, limiting their clinical application and effectiveness in cancer treatment.
Innovation Solution
A method combining a recombinant oncolytic virus with specific mutations and small-molecule anticancer drugs targeting ALK, BTK, EGFR, FGFR, HER2, Parp, PI3K, VEGFR, CDK4/6, or KRAS, along with cytokines, to enhance tumor cell killing and immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wild-type oncolytic viruses are used to infect tumor cells, then tumor cell killing ability is improved, but pathogenicity and tissue damage increase
Solution Approach 1:
The patent extracts and removes the pathogenic components from the wild-type oncolytic virus through genetic modification, creating an attenuated virus that retains tumor-killing ability while eliminating harmful effects on normal tissues. This is achieved by modifying viral genes to reduce virulence while preserving oncolytic properties.
Solution Approach 2:
The patent applies local quality modification by making specific genetic changes at particular locations in the viral genome. These targeted modifications alter the virus's properties locally - reducing pathogenicity in normal tissues while maintaining or enhancing tumor cell specificity and killing ability in malignant cells.
2Object-affected harmful factors
If oncolytic viruses are randomly genetically modified to reduce pathogenicity, then safety is improved, but cytotoxicity and cure rate deteriorate
Solution Approach 1:
The patent systematically changes viral parameters through controlled genetic modification. By adjusting specific genetic parameters and modifying gene expression levels, the virus achieves an optimal balance between reduced pathogenicity and maintained cytotoxicity. This involves precise manipulation of viral genome parameters to achieve desired therapeutic effects.
Solution Approach 2:
The patent creates a composite viral structure by combining modified viral components with specific genetic elements. The attenuated oncolytic virus represents a composite system that integrates safety modifications with therapeutic functionality, creating a hybrid virus that exhibits both reduced harm and enhanced therapeutic effect.
3Ease of operation
If small-molecule anticancer drugs are used alone, then treatment is simple, but drug resistance and inefficiency occur
Solution Approach 1:
The patent merges oncolytic virus therapy with small-molecule anticancer drug treatment to create a combination therapy approach. This integration combines the immunomodulatory and direct cytotoxic effects of the virus with the targeted molecular inhibition provided by small-molecule drugs, achieving synergistic anti-tumor effects that overcome drug resistance while maintaining operational feasibility.
Data Source
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AI summary
The present application relates to the technical field of biomedicine, and in particular to a method for treatment of a tumor by using a recombinant oncolytic virus in combination with a small-molecule anticancer drug. Specifically, the method comprises the following steps: treating a tumor by using a recombinant oncolytic virus in combination with a small-molecule anticancer drug, wherein the small-molecule anticancer drug includes a small-molecule anticancer drug targeting ALK, a small-molecule anticancer drug targeting BTK, a small-molecule anticancer drug targeting EGFR, a small-molecule anticancer drug targeting FGFR, a small-molecule anticancer drug targeting HER2, a small-molecule anticancer drug targeting Parp, a small-molecule anticancer drug targeting PI3K, a small-molecule anticancer drug targeting VEGFR, a small-molecule anticancer drug targeting CDK4/6, and a small-molecule anticancer drug targeting KRAS; and the recombinant oncolytic virus comprises an M protein, a G protein, an N protein, a P protein, and an L protein after site-directed mutagenesis. According to the present application, the recombinant oncolytic virus and the small-molecule anticancer drug are used in combination to attack and kill tumor cells, thereby achieving the synergistic efficacy.