BAFF-R Targeting CAR-T Cells for Drug-Resistant Leukemia
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Solution Overview
Problem
Current treatments for cancers and autoimmune diseases, such as Acute Lymphoblastic Leukemia, are limited by resistance to traditional chemotherapies and the scarcity of suitable donors for hematopoietic stem cell transplantation, necessitating the development of new therapeutic approaches that target B-cell activating factor (BAFF) signaling.
Innovation Solution
Administration of cytotoxic T lymphocytes, natural killer cells, or natural killer T cells engineered to express a chimeric receptor that recognizes BAFF receptors, including BAFF-R, TACI, and BCMA, using sequences with high homology to SEQ ID NOs, which comprises hinge, transmembrane, and intracellular domains, and optionally a signaling peptide, to target and destroy BAFF-expressing cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional chemotherapies are used to treat cancers, then some cancers can be treated, but resistance develops and treatment effectiveness decreases
Solution Approach 1:
The patent uses CAR-T cells as an intermediary biological agent that mediates the immune system's attack on cancer cells. The chimeric receptor on CAR-T cells specifically recognizes and binds to BAFF-R on B-cell malignancies, enabling targeted cytotoxicity without relying on traditional chemotherapeutic agents that induce resistance
Solution Approach 2:
The patent replaces the mechanical/chemical system of traditional chemotherapy with a biological recognition system. The CAR-T cells use molecular recognition (antigen-receptor binding) and biological signaling pathways to eliminate cancer cells, substituting the non-specific chemical damage of chemotherapy with specific biological targeting
2Adaptability or versatility
If hematopoietic stem cell transplantation is used to treat haematological malignancies, then some patients can be treated, but suitable donors are scarce and patient selection is limited
Solution Approach 1:
The patent enables autologous CAR-T cell therapy where a patient's own T cells are harvested, engineered with the chimeric receptor, and reinfused. This self-service approach eliminates the need for external donors, making the therapy applicable to any patient regardless of donor availability or HLA matching
3Measurement precision
If chimeric antigen receptors are engineered to recognize BAFF-R, then specific targeting of B-cell malignancies is achieved, but the complexity of receptor engineering increases
Solution Approach 1:
The chimeric antigen receptor is a composite molecular construct combining the extracellular antigen-binding domain (single-chain variable fragment recognizing BAFF-R), a hinge region, a transmembrane domain, and an intracellular signaling domain. This composite structure integrates multiple functional elements into a single receptor that provides both specific targeting and effective T-cell activation
Solution Approach 2:
The CAR-T cell platform provides multi-functionality: the chimeric receptor simultaneously enables specific recognition of BAFF-R on B-cell malignancies, mediates T-cell activation through intracellular signaling domains, and directs cytotoxic activity against target cells. This universal platform can be adapted to target different antigens by changing only the antigen-binding domain
Data Source
AI summary
The disclosure relates generally to ligand-based chimeric antigen receptor (CAR) cells. More specifically, the CAR cells express B-cell activating factor (BAFF) protein for recognition by a receptor of BAFF on the surface of a cell. CAR cells can include cytotoxic T lymphocytes, natural killer (NK) cells or natural killer T (NKT) cells that express a chimeric receptor that recognizes a receptor of BAFF. The disclosure further relates to methods of treating a variety of conditions, such as cancers and autoimmune diseases, using the disclosed CAR cells.