Modulating Tumor Microenvironment Interactions via CD8 T Cell Gene Editing
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Solution Overview
Problem
Current cancer therapies face challenges in effectively targeting and modulating interactions within the tumor microenvironment to enhance anti-tumor immunity, as existing methods fail to adequately address the complex communication between various cell types and the extracellular matrix, leading to suppressed immune responses.
Innovation Solution
Modification of CD8 T cells to decrease or eliminate the expression and activity of specific proteins like NRP1 and CRTAM, and administration of antagonists targeting interactions such as VEGFB-NRP1, CADM1-CRTAM, and others, to enhance anti-tumor immune responses, combined with genetic modification using CRISPR or other systems to alter T cell function and expression profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing cancer therapies are used, then treatment is provided, but they fail to adequately address complex cell communication in the tumor microenvironment, leading to suppressed immune responses
Solution Approach 1:
The patent extracts and removes specific proteins (NRP1, CRTAM) from T cells that mediate suppressive interactions in the tumor microenvironment. By deleting these specific genes, the therapy removes the harmful signaling pathways while preserving other T cell functions, thereby enhancing anti-tumor immunity without requiring complete redesign of the immune system.
Solution Approach 2:
The patent changes the molecular parameters of T cells by modifying gene expression levels of specific proteins. Through genetic deletion or modulation of NRP1 and CRTAM genes, the therapy alters the signaling capacity of T cells, transforming them from a state of suppressed function to an enhanced anti-tumor state.
2Productivity
If T cell function is enhanced to overcome tumor resistance, then anti-tumor immunity improves, but the complex communication between cell types and extracellular matrix must be adequately addressed
Solution Approach 1:
The patent uses antagonists as intermediary molecules that block specific protein-protein interactions in the tumor microenvironment. These antagonists mediate the disruption of suppressive signaling pathways by preventing ligand-receptor binding, thereby enhancing T cell function without requiring direct manipulation of T cell genetics in all cases.
Solution Approach 2:
The patent segments the complex tumor microenvironment into specific interaction pathways (VEGFB-NRP1, CADM1-CRTAM, TFPI-SDC4, MFGE8-ITGAV, ADAM12-SDC4, CYR61-ITGAV, FN1-FBLN1/ITGB1) and targets each independently. This segmentation allows for precise modulation of specific suppressive pathways while leaving other immune functions intact.
Data Source
AI summary
The present invention is generally directed to identify interacting cells in the tumor microenvironment and using the identified interactions to enhance anti-tumor immunity in cancer. Identified interactions can be modulated using therapeutic agents. Immune cells resistant to suppression can be used for adoptive cell transfer. The present invention is also generally directed to cell types and genes that are correlated to time of tumor growth and tumor size.