Engineered MSCs for Combinatorial Cancer Immunotherapy
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Solution Overview
Problem
Current cancer treatments, such as chemotherapy and immunotherapy, face challenges in delivering multiple therapies simultaneously to achieve maximal efficacy without significant side effects, and in determining appropriate dosing and timing, especially in ovarian cancer where conventional approaches often fail to achieve remission or lead to relapse.
Innovation Solution
A combinatorial cell-based immunotherapy using engineered mesenchymal stem cells (MSCs) that selectively home to tumors, producing multiple effector molecules to modulate tumor-mediated immunosuppressive mechanisms, thereby stimulating anti-tumor immune responses while limiting systemic toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple therapies are delivered simultaneously to achieve maximal efficacy, then anti-tumor effectiveness is improved, but systemic toxicity increases significantly
Solution Approach 1:
The patent divides the multiple therapeutic functions into separate engineered cell types, each expressing specific effector molecules (e.g., cytokines, checkpoint inhibitors, oncolytic viruses). This segmentation allows each cell type to be optimized for its specific function while collectively achieving multi-pathway anti-tumor activity, reducing the need for high doses of each individual therapy that would cause systemic toxicity
Solution Approach 2:
Engineered mesenchymal stem cells (MSCs) serve as intermediary delivery vehicles that selectively home to the tumor microenvironment. These MSCs act as localized factories producing multiple effector molecules in situ, ensuring high concentration of therapeutics at the tumor site while minimizing systemic circulation and associated toxicity
2Adaptability or versatility
If multiple systemically-administered therapies are used, then comprehensive immunomodulation is achieved, but determining appropriate dosing and timing becomes difficult
Solution Approach 1:
The engineered cells are designed to autonomously navigate to the tumor microenvironment and self-regulate their therapeutic activity based on local conditions. The cells express effector molecules in response to tumor-specific signals, eliminating the need for external dosing schedules and timing adjustments by clinicians
Solution Approach 2:
The patent employs a universal platform of engineered MSCs that can be configured to express multiple different effector molecules simultaneously. This multi-functional approach allows comprehensive immunomodulation through multiple pathways (cytokine production, checkpoint inhibition, oncolytic activity) while simplifying administration to a single cell product rather than multiple separate therapies
3Ease of manufacture
If conventional chemotherapy is used to treat ovarian cancer, then initial treatment is provided, but remission is not achieved and relapse occurs within three years
Solution Approach 1:
The patent fundamentally changes the therapeutic parameters from conventional chemotherapy (systemic cytotoxic agents) to engineered cellular therapeutics that deliver multiple immunomodulatory effectors simultaneously. This includes changing the mechanism of action from direct cell killing to immune system activation, and from single-agent to multi-agent therapy, thereby overcoming chemotherapy resistance and achieving durable remission
Data Source
AI summary
Provided herein are methods and compositions for dynamically controlling and targeting multiple immunosuppressive mechanisms in cancer. Some aspects provide cells engineered to produce multiple effector molecules, each of which modulates a different immunosuppressive mechanisms of a tumor, as well as methods of using the cells to treat cancer, such as ovarian, breast, or colon cancer.