Bridged CAR T Cell Targeting for Controlled Tumor Elimination
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Solution Overview
Problem
Existing CAR T cell therapies face challenges with off-target toxicity and unregulated activation, leading to conditions like tumor lysis syndrome and cytokine release syndrome, which can be fatal to patients.
Innovation Solution
A small molecule ligand linked to a targeting moiety by a linker is used to bridge CAR T cells expressing an E2 anti-fluorescein antibody fragment, directing them to cancer cells, thereby reducing off-target toxicity and enhancing control over CAR T cell activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T cells are administered to treat cancer, then tumor elimination is improved, but off-target toxicity increases
Solution Approach 1:
A small molecule ligand linked to a targeting moiety by a linker is introduced as an intermediary component. The small molecule ligand binds to a receptor on cancer cells, the linker connects to a targeting moiety that binds to the CAR T cell receptor, creating a bridge that directs CAR T cells specifically to cancer cells while reducing off-target activation and toxicity.
2Reliability
If CAR T cells are administered to treat cancer, then tumor elimination is improved, but unregulated activation occurs leading to tumor lysis syndrome and cytokine release syndrome
Solution Approach 1:
The system enables dynamic control of CAR T cell activation through the small molecule ligand. The ligand can be administered at controlled doses and timing, allowing activation of CAR T cells to be turned on when needed for tumor elimination and turned off or reduced when toxicity becomes a concern, providing flexibility in managing the therapeutic response.
Solution Approach 2:
The small molecule ligand acts as a controllable intermediary that mediates between the CAR T cells and the cancer cells. By controlling the administration and dosage of the small molecule ligand, the activation of CAR T cells can be regulated, preventing uncontrolled activation that leads to tumor lysis syndrome and cytokine release syndrome while maintaining effective tumor elimination.
3Reliability
If CAR T cells are administered to treat cancer, then tumor elimination is improved, but control over CAR T cell activation is reduced
Solution Approach 1:
The small molecule ligand serves as a controllable intermediary that enables external regulation of CAR T cell activation. By administering the small molecule ligand at specific doses and times, clinicians can control when and how strongly CAR T cells are activated, providing ease of operation and flexibility in managing the therapy.
Solution Approach 2:
The system allows control over CAR T cell activation by changing parameters of the small molecule ligand administration, such as dose, frequency, and timing. These parameter changes enable precise control over the level and duration of CAR T cell activation, improving ease of operation while maintaining effective tumor elimination.
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 reduces off-target toxicity and provides precise control over CAR T cell activation, minimizing adverse effects and improving treatment efficacy.
Implementation Method 1
a small molecule ligand linked to a targeting moiety by a linker is used as a bridge between the cancer and CAR T cells
Implementation Method 2
the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment
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 wherein the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment, and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.