Modified Carrier Cells for Oncolytic Virus Delivery
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Solution Overview
Problem
Oncolytic viruses face challenges in delivering therapeutic amounts to tumors due to immune system elimination, limited delivery efficiency, and intrinsic tumor resistance, with existing carrier cells facing issues like allogeneic immune responses and poor retention in tumor environments.
Innovation Solution
Development of modified carrier cells, such as stem and tumor cells, engineered to express immunosuppressive factors and inhibitors of immune activation, allowing them to evade immune recognition and enhance viral amplification, thereby overcoming immune barriers and improving delivery efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If oncolytic viruses are systemically administered to deliver therapeutic amounts to tumors, then delivery coverage is improved, but the immune system eliminates the viruses before they reach tumors
Solution Approach 1:
The patent uses carrier cells (such as stem cells or immune cells) as intermediaries to deliver oncolytic viruses systemically. These carrier cells protect the viruses from immune elimination in circulation while enabling targeted delivery to tumors. The carrier cells are engineered to express inhibitors of complement proteins and neutralizing antibodies, creating a protective shield that allows the viruses to survive and reach the tumor site effectively.
2Reliability
If carrier cells are used to protect viruses from immune elimination, then virus delivery efficiency is improved, but allogeneic immune responses and poor retention in tumor environments occur
Solution Approach 1:
The carrier cells are pre-engineered before administration to express immunosuppressive factors and inhibitors of immune activation. This preliminary modification ensures that when the carrier cells are introduced into the patient, they are already equipped to suppress allogeneic immune responses and enhance retention in the tumor microenvironment, preventing rejection before it occurs.
Solution Approach 2:
The patent modifies the immunological parameters of the carrier cells by engineering them to express specific immunosuppressive molecules and inhibitors. This changes the immune recognition profile of the carrier cells, allowing them to evade detection and elimination by the host immune system while improving their ability to retain in tumor environments.
3Reliability
If carrier cells are engineered to express immunosuppressive factors, then immune barrier overcoming is improved, but cell complexity increases
Solution Approach 1:
The patent employs universal carrier cell platforms (such as mesenchymal stem cells or other off-the-shelf cell types) that can be engineered with multiple functions simultaneously. These carrier cells are designed to express both immunosuppressive factors for overcoming immune barriers and inhibitors of complement proteins and neutralizing antibodies for protection in circulation. This multi-functional approach allows a single carrier cell type to address multiple challenges in viral delivery.
Data Source
AI summary
Provided herein are carrier cells and virus combinations and methods for treatment of cancers. Also provided are modified carrier cells for such treatment, and methods of selecting carrier cells that are matched to subjects for such treatment.