Adapter-Regulated CAR T Cells for Safer PSMA Tumor Targeting
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Solution Overview
Problem
Current CAR T cell therapies for prostate cancer face significant safety concerns, including targeted destruction of normal tissues and cytokine storms, and are less effective against metastatic prostate cancer, with limited long-term prognosis.
Innovation Solution
Development of small molecule adapter regulated, target specific chimeric antigen receptor bearing T-cells (SMART CARs) that utilize bi-functional molecules to conjugate with CAR T cells, allowing for precise targeting of prostate cancer cells through a prostate-specific membrane antigen, reducing toxicity and enhancing therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current CAR T cell therapies are used to treat prostate cancer, then tumor targeting capability is achieved, but safety concerns arise including targeted destruction of normal tissues and cytokine storms
Solution Approach 1:
The patent introduces a small molecule adapter as an intermediary component that bridges the CAR T cell and the prostate cancer cell. The adapter consists of a CAR binding moiety that binds to the CAR on T cells and a cancer binding moiety that binds to prostate specific membrane antigen on cancer cells. This intermediary structure enables precise targeting while preventing direct activation and harmful effects, thereby resolving the contradiction between tumor targeting capability and safety concerns regarding normal tissue destruction and cytokine storms.
2Reliability
If conventional CAR T cells are used, then antigen binding and signaling functions are achieved, but safety control and response calibration are limited
Solution Approach 1:
The patent implements dynamic control of CAR T cell activation through the small molecule adapter system. The adapter can be introduced or removed, and its concentration can be adjusted, thereby dynamically controlling the activation state and response intensity of CAR T cells. This dynamic approach enables real-time safety control and response calibration, resolving the contradiction between maintaining antigen binding and signaling functions while improving adaptability for safety control.
3Productivity
If standard CAR T cell therapy is administered, then treatment is provided, but customization for multiple targets and precise control is limited
Solution Approach 1:
The patent segments the CAR T cell therapy system into modular components: the CAR T cell, the small molecule adapter with separable binding moieties, and the cancer target antigen. This segmentation allows independent optimization and customization of each component. Different adapter designs can be created for different cancer targets, enabling precise customization for multiple targets while maintaining efficient treatment delivery, thereby resolving the contradiction between productivity and adaptability.
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
SMART CARs provide safer and more effective cancer treatment by calibrating immune responses, preventing side effects, and enabling customization for multiple targets, thus improving treatment outcomes for prostate cancer, including metastatic cases.
Implementation Method 1
The small molecule adapter comprises a chimeric antigen receptor binding moiety and a cancer binding moiety
Data Source
AI summary
In one embodiment, the invention provides a chimeric antigen receptor (CAR) T cell which is conjugated to a bi-functional molecule which is specific for both an extracellular binding domain of the chimeric antigen receptor (CAR) T cell and prostate-specific membrane antigen (PSMA). The chimeric antigen receptor (CAR) T cell contains a T cell signaling domain and the extracellular binding domain of the chimeric antigen receptor (CAR) T cell is not specific for prostate-specific membrane antigen (PSMA). Compositions and methods of treatment using these CAR T cells are also disclosed.