Humanized Anti-BCMA Antibody With High-Affinity Cell Internalization
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Solution Overview
Problem
Current antibodies targeting BCMA lack high affinity, specificity, and biological activity, and induce significant immunogenicity, limiting their effectiveness in treating BCMA-mediated diseases such as multiple myeloma and autoimmune diseases.
Innovation Solution
Development of an anti-BCMA antibody with specific HCDR and LCDR sequences (SEQ ID NO: 3-8) and their mutant variants, optimized for high affinity, specificity, low immunogenicity, and enhanced endocytosis, combined with cytotoxic conjugates for targeted therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibodies targeting BCMA are used, then they can bind to BCMA, but they lack high affinity and specificity
Solution Approach 1:
The patent optimizes antibody binding affinity and specificity by systematically modifying CDR region amino acid sequences through mutagenesis and selection, changing the molecular parameters of the antibody-antigen interaction to achieve high-affinity binding to BCMA
Solution Approach 2:
The patent focuses optimization efforts on the CDR regions (complementarity determining regions) of the antibody, which are the specific local areas responsible for antigen binding, rather than modifying the entire antibody structure uniformly
2Reliability
If conventional anti-BCMA antibodies are used, then they can target BCMA, but they induce significant immunogenicity
Solution Approach 1:
The patent reduces immunogenicity by modifying the antibody's amino acid sequence to increase homology with human antibodies, changing the immunological parameters to make the therapeutic antibody more compatible with the human immune system
Solution Approach 2:
The patent creates humanized or fully human antibody sequences that copy the structural characteristics of endogenous human antibodies, thereby reducing the immune system's recognition of the therapeutic antibody as foreign
3Reliability
If conventional anti-BCMA antibodies are used, then they can provide some biological activity, but they lack enhanced endocytosis and anti-tumor effects
Solution Approach 1:
The patent enhances endocytosis and anti-tumor activity by optimizing specific amino acid residues in the antibody structure that are known to influence cellular internalization and cytotoxic effector functions, systematically changing structural parameters to improve biological performance
Solution Approach 2:
The patent employs iterative cycles of mutagenesis, cell selection, and functional assessment to progressively improve antibody properties, using feedback from binding assays and biological activity tests to guide further optimization rounds
Data Source
AI summary
Provided are an anti-BCMA antibody, an antigen-binding fragment thereof, and a medical use thereof. Further provided are a chimeric antibody and a humanized antibody containing a CDR region of the anti-BCMA antibody, a pharmaceutical composition containing the anti-BCMA antibody or the antigen-binding fragment thereof, and the use of same as an anti-cancer drug and for treating autoimmune diseases. Particularly, provided are a humanized anti-BCMA antibody, and the use of same in the preparation of a drug for treating BCMA-mediated diseases or conditions and the use of same in disease detection and diagnosis.