CAR T Cell Therapy with Small Molecule Linker
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Solution Overview
Problem
Current CAR T cell therapies face challenges such as off-target toxicity and uncontrolled activation, leading to adverse effects like tumor lysis syndrome and cytokine release syndrome.
Innovation Solution
A method involving the administration of a small molecule ligand linked to a targeting moiety by a linker, which acts as a bridge to direct CAR T cells specifically to cancer cells, thereby reducing off-target toxicity and enhancing control over CAR T cell activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If CAR T cells are administered to target and eliminate cancer cells, then tumor elimination efficacy is improved, but off-target toxicity occurs due to attack on normal cells expressing the targeted antigen
Solution Approach 1:
The patent introduces a small molecule ligand as an intermediary that binds to a specific receptor on cancer cells, which then recruits the CAR T cells to the tumor site. This mediator approach allows for more precise targeting and reduces off-target effects compared to direct CAR T cell administration alone.
Solution Approach 2:
The patent employs preliminary action by first administering the small molecule ligand to bind to cancer cell receptors before introducing the CAR T cells. This pre-positioning of the ligand ensures that CAR T cells are directed specifically to tumor sites, reducing off-target toxicity while maintaining elimination efficacy.
2Speed
If CAR T cells are administered to rapidly eliminate cancer cells, then tumor elimination speed is improved, but uncontrolled activation occurs leading to tumor lysis syndrome and cytokine release syndrome
Solution Approach 1:
The small molecule ligand serves as a controllable intermediary that mediates the interaction between CAR T cells and cancer cells. This intermediary approach provides a buffer that allows for more controlled activation compared to direct CAR T cell-cancer cell interaction, reducing the risk of uncontrolled activation and associated syndromes.
Solution Approach 2:
By administering the small molecule ligand before CAR T cells, the system establishes a controlled recruitment mechanism. This preliminary action ensures that CAR T cells are activated in a more regulated manner at the tumor site, reducing the risk of systemic uncontrolled activation and associated harmful effects.
3Duration of action of moving object
If CAR T cells are administered to achieve prolonged activation and expansion, then in vivo proliferation is improved, but control over activation becomes difficult
Solution Approach 1:
The small molecule ligand acts as a controllable intermediary that facilitates CAR T cell recruitment and activation. This mediator approach provides a level of control over the activation process while still allowing for prolonged in vivo proliferation, as the ligand can be designed with appropriate pharmacokinetic properties to sustain targeted activation.
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 effectively reduces off-target toxicity and provides more precise control over CAR T cell activation, improving the safety and efficacy of CAR T cell therapy.
Implementation Method 1
a small molecule ligand linked to a targeting moiety by a linker is used as a bridge between the cancer and the CAR T cells directing the CAR T cells to the cancer
Data Source
AI summary
The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.