Switchable CAR T Cell Kit for Hematological Cancer
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Solution Overview
Problem
Conventional CAR technology for treating hematological cancer faces challenges such as uncontrolled immune responses, severe side effects, tumor escape variants, and limited antigen specificity, restricting its clinical applications.
Innovation Solution
A kit comprising T cells with a switchable chimeric antigen receptor (CAR) and a targeting module with a tag-binding domain, where the targeting module is administered continuously to enhance antigen specificity and reduce side effects by allowing reversible immune response induction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR technology is used to treat hematological cancer, then anti-tumor activity is achieved, but uncontrolled immune responses and severe side effects occur
Solution Approach 1:
The patent applies dynamics by making the CAR system switchable through ligand binding. The CAR-T cells remain inactive until a specific ligand is administered, at which point they become activated. This dynamic on/off control allows the system to provide anti-tumor activity only when needed, avoiding continuous activation and its associated severe side effects like cytokine release syndrome.
Solution Approach 2:
The patent uses an intermediary approach by introducing a soluble ligand as a mediator between the CAR-T cells and the tumor. The ligand acts as a switch that can be administered to activate the CAR-T cells specifically against tumor cells expressing the target antigen, thereby controlling immune response and reducing off-target effects.
2Device complexity
If conventional CAR technology targets a single antigen, then treatment simplicity is maintained, but tumor escape variants develop
Solution Approach 1:
The patent applies universality by designing a CAR system with a universal CAR component that can recognize multiple different antigens through interchangeable ligands. This allows a single CAR-T cell line to be repurposed to target different tumor antigens by simply changing the administered ligand, thereby preventing tumor escape variants while maintaining treatment simplicity.
Solution Approach 2:
The system dynamically adapts its target antigen based on the administered ligand. The CAR-T cells maintain a constant structure but their target specificity changes dynamically according to which ligand is administered, allowing flexibility to counter tumor escape without complex re-engineering.
3Duration of action of stationary object
If continuous CAR T cell activation is maintained, then anti-tumor persistence is improved, but T cell exhaustion occurs
Solution Approach 1:
The patent applies periodic action by administering the ligand in controlled intervals rather than continuously. The ligand can be administered before and after CAR-T cell infusion, creating periodic activation windows that maintain anti-tumor persistence while allowing T cell rest periods to prevent exhaustion.
Solution Approach 2:
The system incorporates feedback control where the ligand administration timing and duration can be adjusted based on patient response and tumor status. This feedback mechanism ensures sustained anti-tumor activity while preventing over-activation and T cell exhaustion.
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
The solution effectively targets hematological cancer cells with reduced side effects and improved persistence of CAR T cells, enabling a more controlled and sustained anti-tumor response.
Implementation Method 1
a first dosage of the targeting module is continuously administered to the subject having hematological cancer... wherein a first dosage of the targeting module is continuously administered to the subject... with a dosage quantity in the range of 0.1 mg/day to 20 mg/day
Implementation Method 2
a T cell comprising a nucleotide sequence encoding a switchable chimeric antigen receptor (CAR)... wherein the switchable CAR comprises a tag-binding domain or tag, an extracellular hinge and a transmembrane domain
Data Source
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AI summary
The present invention relates to a kit for use in the treatment of hematological cancer comprising a T cell comprising a nucleotide sequence encoding a switchable chimeric antigen receptor (CAR) and a targeting module comprising at least one hematological cancer cell-binding domain and a tag-binding domain or a tag, wherein at least one dosage of a clinically effective amount of the T cell is administered to a subject having hematological cancer and wherein a first dosage of the targeting module is continuously administered to the subject.