Chimeric Signaling Molecule T Cells for Hypoxic Tumors
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Solution Overview
Problem
Cancer cells in hypoxic tumor regions are resistant to conventional chemotherapy and radiation due to low oxygen levels, limiting the effectiveness of treatments and leading to treatment failure.
Innovation Solution
Development of metabolically enhanced T cells expressing a chimeric intracellular signaling molecule and armed with bispecific antibodies to improve cytotoxicity and resistance to immunosuppression in tumor microenvironments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy and radiation are used, then treatment can be administered, but effectiveness is reduced in hypoxic tumor regions
Solution Approach 1:
The patent uses bispecific antibodies as intermediary molecules that bridge T cells and tumor cells. The bispecific antibodies have one arm that binds to a tumor antigen and another arm that binds to a T cell marker, thereby mediating the interaction between immune cells and cancer cells in hypoxic environments where conventional therapies fail.
Solution Approach 2:
The patent modifies T cell parameters by introducing chimeric intracellular signaling molecules that change their metabolic and functional properties. These modified T cells exhibit enhanced cytotoxicity and metabolic reprogramming that enables them to function effectively in hypoxic conditions, transforming the T cell's operational parameters to overcome hypoxia-induced resistance.
2Reliability
If T cells are modified to enhance cytotoxicity, then anti-tumor activity improves, but device complexity increases
Solution Approach 1:
The patent segments the T cell modification into distinct functional components: chimeric intracellular signaling molecules for metabolic enhancement, bisspecific antibodies for targeted binding, and T cell receptors for antigen recognition. This modular approach allows each component to be optimized independently while working together to enhance cytotoxicity without overwhelming complexity.
Solution Approach 2:
The modified T cells are designed with multi-functionality to address various challenges in hypoxic tumor environments. The chimeric signaling molecules provide both metabolic reprogramming and survival signals, while the bisspecific antibodies simultaneously mediate T cell engagement with tumor cells and modulate the tumor microenvironment, reducing the need for multiple separate therapeutic agents.
Data Source
AI summary
The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an intracellular signaling molecule in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.