Armed Oncolytic Virus Therapy for Tumor Infiltration
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Solution Overview
Problem
Oncolytic viruses face challenges in accessing cancer cells within tumor nodules in adequate numbers, eliciting anti-virus immune responses, and navigating a highly immunosuppressive tumor environment, which hampers their effectiveness in cancer treatment.
Innovation Solution
The use of oncolytic viruses armed with immunomodulator molecules, such as IL-2 and IL-23, linked to anchoring peptides to enhance tumor infiltration and immune response, combined with adoptive T-cell therapy to expand tumor-infiltrating lymphocytes ex vivo.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If oncolytic viruses are administered to treat cancer, then anti-cancer effects are achieved through cell lysis and immune response, but the viruses face challenges in accessing cancer cells within tumor nodules in adequate numbers
Solution Approach 1:
The patent uses immunomodulator molecules (such as cytokines) as intermediaries to facilitate the interaction between oncolytic viruses and the tumor microenvironment. These molecules help viruses overcome physical and biological barriers in the tumor, enabling better penetration and access to cancer cells within tumor nodules.
Solution Approach 2:
The patent employs oncolytic viruses that can sense and respond to changes in the tumor microenvironment parameters (such as pH, temperature, or specific molecular markers). By detecting these parameter changes, the viruses activate their oncolytic function specifically within the tumor, overcoming the barriers posed by the unique tumor microenvironment.
2Reliability
If oncolytic viruses are used to elicit anti-virus immune responses, then adaptive antitumor immunity is promoted, but anti-virus immune responses reduce viral effectiveness
Solution Approach 1:
The patent employs immunomodulator molecules that create local quality differences in the tumor microenvironment. These molecules locally suppress anti-virus immune responses within the tumor while allowing adaptive antitumor immunity to develop, thereby resolving the contradiction between eliciting immune responses and avoiding viral neutralization.
Solution Approach 2:
The patent uses immunomodulator molecules to perform preliminary actions by pre-conditioning the tumor microenvironment before oncolytic virus administration. This preliminary modulation of the immune landscape reduces pre-existing anti-virus immunity and facilitates subsequent viral effectiveness while maintaining the ability to elicit adaptive antitumor immunity.
3Ease of operation
If oncolytic viruses navigate a highly immunosuppressive tumor environment, then tumor infiltration is improved, but the immunosuppressive environment hampers viral effectiveness
Solution Approach 1:
The patent uses immunomodulator molecules as intermediaries to mediate between the oncolytic viruses and the immunosuppressive tumor environment. These molecules counteract immunosuppressive signals and create a more favorable environment for viral replication and function, thereby improving both tumor infiltration and viral effectiveness simultaneously.
Data Source
AI summary
The presently disclosed subject matter relates to tumor infiltrated T cells induced by oncolytic virus (“OV-induced T cells”), methods of making and using said OV-induced T cells for an adoptive T-cell therapy. The presently disclosed subject matter further relates to oncolytic viruses and armed oncolytic viruses, methods of making and using said oncolytic viruses, as well as pharmaceutical compositions and kits comprising said oncolytic viruses.