BCMA-Targeting CAR-T Cell Therapy for Multiple Myeloma
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Solution Overview
Problem
Current treatments for multiple myeloma, a type of blood cancer, often face relapse and secondary resistance, necessitating an effective immunotherapeutic agent that can specifically target BCMA-expressing tumor cells.
Innovation Solution
A chimeric antigen receptor (CAR) targeting BCMA is developed, comprising a BCMA-binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signal transduction domain, expressed in CAR-T cells, using a humanized anti-BCMA antibody to specifically bind and kill BCMA-expressing cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments (chemotherapy, radiation therapy, stem cell transplantation) are used for multiple myeloma, then initial treatment effectiveness is achieved, but patients experience relapse and secondary resistance
Solution Approach 1:
The patent changes the therapeutic approach from conventional chemotherapy to CAR-T cell therapy with modified parameters including humanized anti-BCMA antibody design, specific CAR structure configuration, and optimized costimulatory domains to achieve sustained remission and overcome relapse
Solution Approach 2:
The patent creates a copy of the successful CAR-T approach used in B-cell non-Hodgkin's lymphoma and adapts it for multiple myeloma by targeting BCMA, replicating the immunotherapeutic mechanism in a different disease context
2Measurement precision
If CAR-T cells are developed to specifically target BCMA-expressing tumor cells, then treatment specificity is improved, but development complexity and time increase
Solution Approach 1:
The CAR structure is segmented into distinct functional domains: humanized anti-BCMA antibody for antigen recognition, transmembrane domain for cell membrane anchoring, costimulatory domains for T cell activation, and intracellular signaling domains for signal transduction, allowing optimized design of each component
Solution Approach 2:
The patent uses humanized anti-BCMA antibody as an intermediary component that specifically binds to BCMA on tumor cells, mediating the recognition and activation process between CAR-T cells and target cells
3Productivity
If humanized anti-BCMA antibody is used in CAR construction, then immune response effectiveness is improved, but manufacturing and characterization difficulty increase
Solution Approach 1:
The patent copies the successful humanized antibody approach from other immunotherapies and applies it to anti-BCMA CAR construction, utilizing established humanization techniques and frameworks to simplify the manufacturing process
Solution Approach 2:
The patent changes the antibody origin from murine to humanized, modifying parameters including amino acid sequences, CDR regions, and framework regions to improve immune response while maintaining manufacturability through standardized human antibody expression systems
Data Source
AI summary
An antibody specifically binding to BCMA (B-cell maturation antigen) or fragment thereof, including: a heavy chain variable region including a CDR1 region represented by the amino acid sequence of SEQ ID NO: 1, a CDR2 region represented by the amino acid sequence of SEQ ID NO: 2, and a CDR3 region represented by the amino acid sequence of SEQ ID NO: 3; and a light chain variable region including a CDR1 region represented by the amino acid sequence of SEQ ID NO: 4, a CDR2 region represented by the amino acid sequence of SEQ ID NO: 5, and a CDR3 region represented by the amino acid sequence of SEQ ID NO: 6.