Pluripotent Stem Cell-Derived CAR T Cells for Tumor Targeting
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Solution Overview
Problem
Current adoptive T cell therapies for cancer are limited by the rarity of antigen-specific T cells, their short lifespan, and inability to overcome tumor immunoescape mechanisms, making it difficult to generate sufficient functional T cells for effective immunotherapy, especially in immunodeficient patients and across immunogenic barriers.
Innovation Solution
Engineering pluripotent stem cells, such as embryonic stem cells or induced pluripotent stem cells, to express chimeric antigen receptors (CARs) that allow T cells to target specific antigens independently of HLA, enhancing survival, functional potential, and cytotoxic activity, enabling 'off-the-shelf' T cell administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current adoptive T cell therapies are used, then treatment can be provided to some patients, but the therapy is limited by the rarity of antigen-specific T cells, their short lifespan, and inability to overcome tumor immunoescape mechanisms
Solution Approach 1:
The patent applies preliminary action by pre-engineering pluripotent stem cells with chimeric antigen receptors and tumor-targeting capabilities before differentiation. This allows T cells to be prepared in advance with enhanced functionality, overcoming the limitation of having to rely on rare naturally occurring antigen-specific T cells from patients
Solution Approach 2:
The patent changes key parameters of T cells by engineering them to express chimeric antigen receptors that recognize multiple tumor antigens simultaneously. This multi-targeting capability fundamentally alters the T cells' ability to overcome tumor immunoescape mechanisms, transforming them from single-antigen specific to multi-antigen reactive
2Measurement precision
If T cells are engineered to target specific antigens, then specificity is improved, but the complexity of generation and HLA matching requirements increase
Solution Approach 1:
The patent applies universality by creating T cells that can target multiple tumor antigens through chimeric antigen receptors. These engineered T cells are designed to recognize various tumor-associated antigens simultaneously, making them universally applicable across different tumor types and patients without requiring HLA matching
Solution Approach 2:
The patent uses chimeric antigen receptors as intermediaries that bridge the gap between T cells and tumor antigens. These CARs contain antibody-derived binding domains that directly recognize tumor surface antigens without requiring HLA presentation, thereby simplifying the generation process by eliminating HLA matching requirements
3Adaptability or versatility
If traditional T cell sources are used, then patient-specific treatment is possible, but the number of available T cells is insufficient for effective therapy
Solution Approach 1:
The patent applies preliminary action by pre-expanding and pre-engineering T cells from pluripotent stem cells before adoption. This allows sufficient numbers of functional T cells to be generated in advance, overcoming the productivity limitation of traditional approaches that rely on scarce patient-derived T cells
Solution Approach 2:
The patent uses induced pluripotent stem cells as a renewable source that can be expanded indefinitely in culture. These iPSCs serve as a copyable template for generating large numbers of T cells, replacing the limited supply of patient-derived T cells while maintaining patient-specificity through autologous iPSC derivation
Data Source
AI summary
The present invention relates to the field of adoptive immunotherapy. The invention provides methods for generating phenotypically defined, functional, and/or expandable T cells from pluripotent stem cells engineered through safe genetic modifications. The engineered cells may provide one or more of: 1) targeting a specific predetermined antigen expressed on the cell surface of a target cell in an HLA independent manner, 2) enhanced survival and functional potential 3) “off-the-shelf” T cells for administration to multiple recipients, eventually across immunogenic barriers, and/or 4) cytotoxic potential and anti-tumor activity.