TCR-Deficient T Cells for Targeted Cancer Elimination
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Solution Overview
Problem
Current cancer therapies are inadequate as they often fail to selectively target cancer cells, are not permanent, and are not cost-effective, while T cell-based immunotherapies face challenges in robustness and timing due to the need for patient-specific customization and the limitations of immune cell function in cancer patients.
Innovation Solution
Development of TCR-deficient T cells that lack functional T cell receptors, which can be engineered to express non-TCR receptors like chimeric NKG2D, allowing them to target cancer cells without inducing adverse immune responses, and can be produced in advance for widespread use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cell-based immunotherapy is used to target cancer cells, then cancer cell elimination is achieved, but the therapy is not permanent and relapse occurs
Solution Approach 1:
The patent applies preliminary action by pre-modifying T cells ex vivo to express chimeric receptors with enhanced anti-cancer activity and memory potential. These modified T cells are then infused into patients, where they persist long-term and provide durable immunity. The ex vivo modification allows the T cells to be prepared in advance with optimized characteristics before administration, enabling lasting cancer remission without requiring continuous therapy.
2Reliability
If patient-specific customized T cell therapy is developed, then treatment effectiveness is improved, but production time and cost increase
Solution Approach 1:
The patent applies parameter changes by modifying T cell characteristics through controlled genetic engineering parameters. Specifically, T cells are modified to express chimeric receptors with specific binding affinities and signaling properties. By optimizing these molecular parameters during ex vivo modification, the therapy achieves high effectiveness while the modified cells can be produced in standardized batches, reducing the time and cost associated with fully customized patient-specific therapies.
3Reliability
If conventional T cell therapy is used, then cancer targeting is achieved, but healthy cells are harmed and adverse immune responses occur
Solution Approach 1:
The patent applies local quality by creating T cells with chimeric receptors that have specific binding affinities for cancer cell markers while maintaining compatibility with healthy tissue. The chimeric receptor structure allows the T cells to recognize and target cancer cells with high specificity, while the modified T cell composition reduces harmful effects on healthy cells. This localized specificity at the receptor-ligand interaction level enables effective cancer targeting without widespread damage to normal tissues.
4Object-affected harmful factors
If TCR-deficient T cells are engineered to express non-TCR receptors, then adverse immune responses are reduced, but the complexity of cell engineering increases
Solution Approach 1:
The patent applies the taking out principle by removing or reducing the endogenous TCR from the T cell composition while introducing a chimeric receptor that performs the necessary cancer targeting function. This extraction of the problematic TCR component eliminates the source of adverse immune responses, while the chimeric receptor provides the required anti-cancer activity. The process involves selective removal of TCR-expressing cells or molecular modification to eliminate functional TCRs, followed by introduction of the alternative chimeric receptor system.
Data Source
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AI summary
The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.