Placenta-Derived Allogeneic CAR-T Cells for Universal Cancer Therapy
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Solution Overview
Problem
CAR therapies for cancer are expensive and limited in availability due to the need for patient-specific cell harvesting and processing, making them inaccessible to many who need them.
Innovation Solution
Development of an allogeneic CAR therapy using placenta-derived T cells, which are genetically modified to reduce alloreactivity and expanded for therapeutic use, offering a more accessible and effective treatment option.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If autologous CAR-T therapy is used with patient-specific cells, then treatment efficacy is improved, but cost and complexity increase significantly
Solution Approach 1:
The patent uses placenta-derived T cells as a universal donor source that can be copied and used for multiple patients without requiring individual patient cell harvesting and processing. This creates a standardized, off-the-shelf product that maintains therapeutic efficacy while eliminating the complex personalized manufacturing process
Solution Approach 2:
The patent develops a universal allogeneic CAR-T cell product derived from placenta that can treat multiple patients with different cancers. The cells are engineered with modified TCR genes to reduce alloreactivity, making them universally applicable across different patients without requiring patient-specific customization
2Reliability
If patient-specific cell harvesting and processing is performed, then treatment effectiveness is improved, but accessibility and availability worsen
Solution Approach 1:
The patent performs preliminary actions by harvesting and processing T cells from placenta donors in advance, creating a bank of ready-to-use allogeneic CAR-T cells. These pre-prepared cells can be immediately administered to patients without requiring individual patient cell collection and processing at the time of treatment
Solution Approach 2:
The patent creates a universal cell product that can be copied and distributed to multiple patients. The placenta-derived T cells serve as a reusable source that can be expanded and used for numerous treatments, making the therapy accessible at multiple centers without requiring each center to perform complex cell processing
3Device complexity
If allogeneic CAR-T cells are used to reduce complexity, then manufacturing cost decreases, but alloreactivity and GVHD risk increase
Solution Approach 1:
The patent extracts and removes the problematic TCR genes from the allogeneic T cells through genetic modification. By knocking out the TCR alpha constant gene, the cells lose their ability to recognize and react against host HLA molecules, thereby eliminating alloreactivity while maintaining the benefits of allogeneic therapy
Solution Approach 2:
The patent converts the potential harm of alloreactivity into a benefit by using genetic modification to create T cells that are specifically designed to be non-alloreactive. The engineered cells maintain robust anti-tumor activity while the modified TCR status prevents harmful immune reactions against the patient's tissues
4Object-affected harmful factors
If TCR gene modification is performed to reduce alloreactivity, then GVHD risk decreases, but cell functionality may be affected
Solution Approach 1:
The patent applies local quality modification by specifically targeting and modifying only the TCR alpha constant gene while leaving the rest of the T cell genome and CAR expression intact. This localized genetic modification selectively eliminates alloreactivity while preserving the cells' anti-tumor functions and CAR-mediated cytotoxicity
Data Source
AI summary
The present invention discloses populations of T cells expressing a chimeric antigen receptor (CAR), wherein said T cells are placental T cells derived from cord blood, placental perfusate, or a mixture thereof. Such populations of cells are shown to be improved in a number of aspects over alternative populations of cells such as those derived from peripheral blood mononuclear cell T cells. It also discloses methods of treating cancer, such as a hematologic cancer, e.g., a B cell cancer, or a symptom thereof in a patient in need thereof. These methods comprise administering to the patient an amount of the population of T cells of any one of the invention effective to alleviate the cancer or symptom thereof in the patient.