Ex Vivo Bite-Activated T Cells via pICF-Mediated Trogocytosis
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Solution Overview
Problem
Existing adoptive cell therapies for cancer, such as ACT, face challenges with off-target activation of T cells and the selection of antigens that may target non-cancer tissues, necessitating a method to optimize T cell subsets for effective cancer therapy with minimized adverse effects.
Innovation Solution
The generation of cancer-killing T cells is enhanced by optimizing the proximity between T cells and cancer cells using a proximity immuno-coaching factor (pICF), allowing T cells to acquire cancer cell surface markers and become trogocytotic T cells, which are then enriched and administered to patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cells are activated using conventional adoptive cell therapy methods, then tumor-specific lymphocytes are generated, but off-target activation occurs and non-cancer tissues are targeted
Solution Approach 1:
The patent uses a proximity immuno-coaching factor (pICF) as an intermediary molecule that bridges the T cell and cancer cell. The pICF binds to both the T cell receptor and a ligand on the cancer cell surface, facilitating specific interaction only between T cells and cancer cells while preventing off-target activation of normal tissues.
Solution Approach 2:
The invention enables T cells to acquire cancer cell surface markers through trogocytosis, making the T cells locally adapted to recognize and target specific cancer cell characteristics. This local quality transfer ensures that activated T cells are highly specific to the cancer type rather than broadly activated against all tissues expressing similar antigens.
2Quantity of substance
If T cells are expanded ex vivo to increase therapeutic dosage, then more cancer-killing T cells are available, but the complexity of cell selection and expansion increases
Solution Approach 1:
The patent performs preliminary activation of T cells ex vivo using the pICF before administration to the patient. This preliminary action ensures that only properly activated and cancer-specific T cells are expanded and administered, simplifying the overall process by eliminating the need for complex post-administration activation protocols.
Solution Approach 2:
The invention changes the activation parameters of T cells by using pICF-mediated proximity coaching instead of conventional activation methods. This parameter change allows for more controlled and specific activation, reducing the complexity of cell selection while maintaining high activation efficiency.
3Adaptability or versatility
If conventional T cell activation methods are used, then T cells can be generated, but the effectiveness against diverse cancer types is limited
Solution Approach 1:
The pICF is designed with universal applicability to work across diverse cancer types by targeting conserved cancer cell surface features or by being adaptable to different cancer-specific antigens. This universality allows the same basic mechanism to effectively activate T cells against various cancer types while maintaining consistent killing activity through the standardized pICF-mediated activation process.
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 results in highly effective cancer therapies that selectively target diverse cancer types, including solid and hematological cancers, with reduced off-target effects and personalized treatment options.
Implementation Method 1
allowing T cells to acquire cancer cell surface markers and become trogocytotic T cells
Data Source
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AI summary
Generation and identification of highly effective immune effector cell in terms of target cell-killing activity can be enhanced by optimizing the proximity between a target cell and the immune effector cell. The cancer-killing T cells described herein can provide highly effective therapies for diverse cancer types, e.g., solid cancers, hematological cancers, and metastatic forms thereof. Provided herein are ex-vivo methods of generating cancer-killing T cells, compositions comprising such immune cells; methods of using the cells, methods of selecting optimal agents for enhancing the target cell killing activity, methods of selecting an optimized immune cell and methods of using this approach to evaluate patient responsiveness to other cancer therapies.