Genetically Engineered Cells for Tumor Microenvironment Rebalancing
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Solution Overview
Problem
Existing immunotherapeutic strategies for targeting metastatic tumors are limited by immunosuppression in the tumor and pre-metastatic tumor microenvironment, and there is a need for effective methods to rebalance dysregulated physiological microenvironments to treat primary tumors, prevent metastasis, and improve immunotherapy.
Innovation Solution
Genetically engineered myeloid and mesenchymal cells expressing proteins encoded by exogenous mRNA, such as IL12, IL6 decoy receptor, CD40L, sTREM2, TIMPs, and TGFβRII, are introduced to modulate tumor, immune, and neurological microenvironments, using methods like electroporation and lentiviral transduction to achieve transient protein expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapeutic strategies are used to target metastatic tumors, then immune response against tumors is enhanced, but immunosuppression in the tumor and pre-metastatic tumor microenvironment limits effectiveness
Solution Approach 1:
The patent uses genetically engineered myeloid and mesenchymal cells as intermediary carriers to deliver exogenous mRNA encoding immune-modulating proteins (IL12, IL6DR, CD40L, sTREM2, TIMPs, TGFβRII) directly into the tumor and pre-metastatic microenvironment. These cells act as mediators that locally produce therapeutic proteins to counteract immunosuppression while enhancing anti-tumor immunity, thereby resolving the contradiction between enhancing immune response and overcoming microenvironmental immunosuppression
Solution Approach 2:
The patent changes the physiological parameters of the tumor microenvironment by introducing exogenous mRNA that encodes proteins capable of modulating immune responses. The engineered cells alter local concentrations of cytokines and immune regulators (through IL12 production, IL6 decoy reception, CD40L expression, etc.), transforming the immunosuppressive microenvironment into an immunostimulatory one that supports effective anti-tumor immunity
2Reliability
If genetically engineered cells are introduced to modulate microenvironments, then rebalancing of dysregulated physiological microenvironments is achieved, but complexity of the treatment method increases
Solution Approach 1:
The patent employs universal myeloid and mesenchymal cell platforms that can be engineered to express multiple different therapeutic proteins encoded by exogenous mRNA. These cell types serve as multi-functional vectors capable of delivering various immune-modulating agents (cytokines, decoy receptors, ligands, inhibitors) to different microenvironments (tumor, immune, neurological), reducing the need for separate engineered cell lines for each therapeutic agent and thereby managing complexity while maintaining rebalancing 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
The engineered cells effectively rebalance dysregulated microenvironments, enhancing immune response against tumors and preventing metastasis, while improving the efficacy of immunotherapy.
Implementation Method 1
using methods like electroporation and lentiviral transduction to achieve transient protein expression
Implementation Method 2
using methods like electroporation and lentiviral transduction to achieve transient protein expression
Data Source
AI summary
In aspects, the disclosure provides genetically engineered cells, uses of the cells, and methods of making the cells.