Engineered T Cells Knockout SIT1 BST2 PD-1
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Solution Overview
Problem
Current cellular immunotherapy for cancer, particularly in solid tumors, faces limitations due to immunosuppression in the tumor microenvironment, leading to reduced therapeutic efficacy.
Innovation Solution
The modification of immune cells, such as T cells and tumor-infiltrating lymphocytes, by knocking out or knocking down genes like SIT1, BST2, and PD-1 using CRISPR or RNA interference, to enhance their resistance to immunosuppression and improve their ability to target cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune cells are used for adoptive cell therapy, then cancer treatment is provided, but immunosuppression in the tumor microenvironment reduces therapeutic efficacy
Solution Approach 1:
The patent extracts and removes harmful immunosuppressive factors by knocking out specific genes (SIT1, BST2, PD-1) in the immune cells. This genetic modification eliminates the molecules that would otherwise allow tumor cells to suppress the immune response, thereby enhancing the therapeutic efficacy of adoptive cell therapy.
Solution Approach 2:
The patent converts the harmful immunosuppressive molecules into beneficial targets for modification. By identifying and knocking out genes that encode immunosuppressive proteins (SIT1, BST2, PD-1), the therapy transforms cells that would normally be suppressed by tumors into enhanced anti-tumor effectors, turning a vulnerability into a therapeutic advantage.
2Reliability
If multiple genes are knocked out in immune cells, then resistance to immunosuppression is improved, but device complexity increases
Solution Approach 1:
The patent segments the complex task of overcoming immunosuppression into targeting three specific genes (SIT1, BST2, PD-1) rather than attempting to modify the entire genome or multiple unrelated pathways. This segmentation allows for focused, manageable genetic modifications that collectively achieve robust resistance to immunosuppression.
Solution Approach 2:
The patent uses CRISPR-Cas9 technology as a universal platform to knock out multiple different genes (SIT1, BST2, PD-1) using the same core mechanism. This multi-functional approach allows a single gene-editing system to address multiple immunosuppressive pathways simultaneously, reducing overall complexity compared to using different methods for each gene.
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
This approach enhances the therapeutic efficacy of adoptive cell therapy by overcoming immunosuppression in the tumor microenvironment, allowing immune cells to more effectively kill cancer cells, thereby improving treatment outcomes for cancer patients.
Implementation Method 1
The modification may be of any kind, including by CRISPR or RNA interference, for example.
Implementation Method 2
The modification may be of any kind, including by CRISPR or RNA interference, for example.
Data Source
AI summary
Embodiments of the disclosure encompass methods and compositions related to cell therapy treatment, including for cancer. In specific embodiments, the disclosure concerns adoptive cell therapy cancer treatment in which tumor-1 infiltrating lymphocytes and/or engineered T cells are modified to increase their efficacy as a cancer treatment. In specific cases, the cells are engineered for knock out of one or more genes, such as Signaling Threshold Regulating Transmembrane Adaptor 1 (SIT1), Bone Marrow Stromal Cell Antigen 2 (BST2), and/or programmed cell death protein 1 (PD-1).