Fully Humanized Anti-BCMA scFv Antibody Engineering
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Solution Overview
Problem
There is a need for new BCMA-specific binding molecules that can target BCMA on tumor cells with high specificity and affinity, particularly for the treatment of multiple myeloma, while minimizing side effects.
Innovation Solution
Development of fully humanized single-chain antibodies and their recombinant scFv-hFc molecules that bind to BCMA with high affinity, specifically designed to target BCMA on tumor cells, utilizing genetic engineering and yeast display to create antibodies with optimized binding properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If fully humanized single-chain antibodies are developed to target BCMA on tumor cells, then specificity and affinity for BCMA is improved, but complexity of antibody engineering and production increases
Solution Approach 1:
The patent segments the antibody structure into variable regions (VH and VL) that can be independently engineered and combined. The single-chain antibody format separates the antigen-binding function from the Fc region, allowing focused optimization of BCMA binding while simplifying production. The variable regions are further segmented into CDRs (complementarity determining regions) that can be individually optimized for affinity and specificity.
Solution Approach 2:
The patent uses yeast display technology as an intermediary system to facilitate antibody engineering. The scFv antibodies are expressed on the surface of yeast cells, serving as a platform for high-throughput screening and selection of anti-BCMA antibodies with optimized properties. This intermediary system enables systematic evaluation and selection of antibody variants without requiring complex mammalian cell culture for each iteration.
2Weight of moving object
If single-chain antibody format is used instead of intact antibody, then molecular weight is reduced and tissue penetration is improved, but antigen-binding activity may be compromised
Solution Approach 1:
The patent merges the heavy chain variable region (VH) and light chain variable region (VL) into a single polypeptide chain connected by a linker peptide. This merging creates the single-chain Fv (scFv) format that maintains the essential antigen-binding site while eliminating the need for separate heavy and light chains. The linker enables proper spatial arrangement of VH and VL domains to form functional antigen-binding sites.
Solution Approach 2:
The patent optimizes the linker peptide parameters (length, composition, flexibility) to ensure proper folding and stability of the scFv structure. By adjusting linker parameters, the antibody maintains high affinity binding to BCMA despite the simplified single-chain format. The variable region sequences are also optimized to ensure stable folding and high-binding activity in the single-chain context.
Data Source
AI summary
The invention relates to a novel antibody and an antibody fragment thereof specifically binding to a B-cell maturation antigen (BCMA), and particularly relates to a fully humanized single-chain variable fragment (scFv). The invention further relates to a nucleic acid encoding the antibody, a vector, and a host cell expressing the nucleic acid. Furthermore, the invention also relates to a composition containing the antibody described herein, and use thereof in treatment and diagnosis.