Inactivated MVA Virus for Solid Tumor Immunotherapy
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Solution Overview
Problem
Current cancer treatments, particularly for melanoma, face challenges in activating the immune system to target tumor cells due to immune evasion mechanisms employed by tumors, leading to resistance against conventional therapies and limited effectiveness of immune checkpoint blockade therapies.
Innovation Solution
The use of inactivated Modified Vaccinia Ankara (MVA) virus, either heat-inactivated or UV-inactivated, is delivered to tumor cells to induce an immune response by activating the cytosolic DNA-sensing pathway, combined with immune checkpoint blocking agents to enhance anti-tumor immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer therapies are used, then treatment is administered, but tumors are inherently resistant leading to treatment failure
Solution Approach 1:
The patent uses inactivated MVA virus as an intermediary agent that delivers tumor antigens to the immune system. The virus acts as a carrier that presents tumor-specific antigens to dendritic cells and T cells, bridging the gap between tumor cells and the immune response, thereby overcoming tumor resistance to conventional therapies
Solution Approach 2:
The patent enables the immune system to fight the tumor itself by inducing endogenous antigen presentation. The inactivated MVA virus stimulates the immune system to recognize and attack tumor cells expressing the delivered antigen, allowing the body's own immune mechanisms to overcome tumor resistance
2Reliability
If immune checkpoint blockade therapy is used, then immune activation is attempted, but tumor immune evasion mechanisms limit effectiveness
Solution Approach 1:
The patent applies preliminary action by first delivering tumor antigens via inactivated MVA virus to prime the immune system and establish antigen-specific T cell responses before or alongside immune checkpoint blockade therapy. This preliminary antigen presentation ensures that when checkpoint inhibitors are administered, there are already activated T cells ready to attack the tumor, countering immune evasion
Solution Approach 2:
The patent employs preliminary anti-action by using inactivated MVA virus to pre-activate the immune system against tumor antigens, creating an immune response that opposes the tumor's immune evasion mechanisms. This pre-established immune activation counteracts the suppressive effects of checkpoint proteins before they can fully inhibit anti-tumor immunity
3Reliability
If inactivated MVA virus is delivered to induce immune response, then anti-tumor immunity is enhanced, but complex viral modification and inactivation processes are required
Solution Approach 1:
The patent extracts only the essential immunogenic components of the MVA virus while removing replication-competent elements through inactivation. By using inactivated MVA virus, the patent separates the beneficial antigen-delivery and immune-stimulating functions from the harmful replication and potential pathogenicity, simplifying the therapeutic approach while maintaining efficacy
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
This approach effectively increases cytotoxic CD8+ T cells, reduces immune suppressive CD4+ T cells, and induces type I IFN production, leading to tumor reduction, eradication, and inhibition of metastasis, with potential for systemic anti-tumor immunity.
Implementation Method 1
an amount of inactivated-MVA, such as heat-inactivated-MVA
Implementation Method 2
such as heat-inactivated-MVA or UV-inactivated-MVA
Data Source
AI summary
The present disclosure relates to infection-competent, but nonreplicative inactivated modified vaccinia Ankara (MVA) and its use as immunotherapy, alone, or in combination with immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to inducing an immune response in a subject diagnosed with a solid malignant tumor.