CAR-T Cells Co-Expressing VIP Antagonists for Solid Tumor Therapy
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Solution Overview
Problem
Current CAR therapies are less effective in treating solid tumors, particularly due to the immunosuppressive tumor microenvironment, which includes high levels of vasoactive intestinal peptide (VIP) that suppress T cell activity.
Innovation Solution
The use of CAR-expressing immune cells co-expressing a vasoactive intestinal peptide receptor antagonist, which competes with endogenous VIP for receptor binding, thereby enhancing T cell activation and proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR therapies are used to treat solid tumors, then T cell activation is stimulated, but T cell activity is suppressed by high levels of VIP in the tumor microenvironment
Solution Approach 1:
The patent introduces a VIP receptor antagonist as an intermediary substance that blocks the interaction between VIP and its receptor on T cells. This antagonist acts as a mediator to prevent VIP from binding to and suppressing T cell activity, thereby resolving the contradiction between CAR therapy activation and VIP-mediated suppression without directly modifying the CAR structure itself
Solution Approach 2:
The patent applies preliminary anti-action by pre-treating T cells with VIP receptor antagonists before administering CAR therapy. This preliminary blocking of VIP receptors prevents the subsequent suppressive effect of VIP on activated T cells, ensuring that the CAR-induced activation is not subsequently inhibited by the immunosuppressive tumor microenvironment
2Productivity
If T cells are activated to attack cancer cells, then cancer cell lysis is enhanced, but T cell persistence in the tumor microenvironment is reduced due to immunosuppression
Solution Approach 1:
The VIP receptor antagonist serves as a protective intermediary that shields activated T cells from VIP-mediated suppression in the tumor microenvironment. By blocking the VIP-receptor interaction, the antagonist enables T cells to maintain their activated state and persist longer in the tumor site, thereby resolving the contradiction between enhanced cancer cell lysis and reduced T cell persistence
Solution Approach 2:
The patent applies beforehand cushioning by pre-equipping T cells with VIP receptor antagonists before they encounter the immunosuppressive tumor microenvironment. This prior protection cushions T cells against the suppressive effects of VIP, allowing them to maintain functionality and persistence throughout their therapeutic action against cancer cells
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 expansion and proliferative capacity of CAR-expressing cells, improves their efficacy in targeting and lysing cancer cells, and increases their persistence in the tumor microenvironment.
Implementation Method 1
co-expressing a vasoactive intestinal peptide receptor antagonist, which competes with endogenous VIP for receptor binding
Data Source
AI summary
This disclosure relates to compositions and methods of treating disorders such as cancer using immune effector cells (e.g., T cells or NK cells) that express a chimeric antigen receptor (CAR). In certain embodiment, this disclosure relates to methods of using a CAR-expressing cell therapy in combination with a vasoactive intestinal peptide receptor antagonist.