BCMA-Targeting CAR T Cell Receptor Engineering
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Solution Overview
Problem
Current therapies for hematologic malignancies, particularly those targeting B-cell maturation antigen (BCMA), have shown varying effectiveness with undesired side effects, necessitating the development of novel and improved treatments.
Innovation Solution
The development of chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) that specifically bind to BCMA, comprising specific amino acid sequences in their variable regions, enabling targeted immunotherapy for cancer treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies targeting BCMA are used, then cancer cells can be targeted, but undesired side effects occur and effectiveness varies
Solution Approach 1:
The patent applies local quality by designing CARs and TCRs with specific amino acid sequences in their variable regions (VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, VL CDR3) that are optimized to bind specifically to BCMA on cancer cells. This localized optimization of binding specificity reduces off-target effects while improving effectiveness against BCMA-expressing hematologic malignancies
Solution Approach 2:
The patent employs parameter changes by modifying the amino acid sequences of the antigen-binding molecules, specifically optimizing the complementarity determining regions to enhance binding affinity and specificity for BCMA. These sequence variations (with specific amino acids at defined positions) tune the interaction parameters to achieve better therapeutic outcomes with reduced side effects
2Reliability
If T cells are engineered to express CARs or TCRs with specific binding domains, then the ability to target cancer cells is enhanced, but the complexity of the therapy increases
Solution Approach 1:
The patent applies segmentation by dividing the antigen-binding molecule into distinct complementarity determining regions (VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, VL CDR3), each with specific amino acid sequences that can be independently optimized. This modular approach allows systematic engineering of T cells with tailored binding specificities while managing therapeutic complexity
Solution Approach 2:
The patent achieves universality by creating CARs and TCRs with standardized structural frameworks that can target BCMA across different hematologic malignancies. The conserved amino acid sequences at key positions provide universal binding capability, while allowing adaptation to different cancer types expressing BCMA, thereby reducing overall therapy complexity through a platform approach
Data Source
AI summary
The invention provides antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs), and engineered T cell receptors, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.