CD33-Binding Proteins for AML Targeting
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Solution Overview
Problem
Current therapies for Acute Myeloid Leukemia (AML) targeting CD33 antigen are limited, with a need for additional CD33 binding domains for both therapeutic and diagnostic purposes due to the disease's heterogeneous nature and low long-term survival rates.
Innovation Solution
Development of isolated proteins comprising specific heavy chain and light chain complementarity determining regions (CDRs) that bind CD33, including scFv, Fab, and VHH formats, designed to target CD33 for therapeutic and diagnostic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies targeting CD33 are used, then some therapeutic effect is achieved, but treatment outcomes are limited due to AML heterogeneity and low long-term survival rates
Solution Approach 1:
The patent develops multiple CD33 binding domains (scFv, Fab, VHH formats) that can be used across different therapeutic platforms (CARs, bispecific antibodies, antibody-drug conjugates), creating a universal building block that adapts to various treatment strategies for heterogeneous AML subtypes
Solution Approach 2:
The invention segments the CD33 targeting approach into modular binding domains (heavy chain variable region sequences SEQ ID NOs: 18-27) that can be independently combined with different constant regions and functional elements, allowing customization for specific AML heterogeneity patterns
2Adaptability or versatility
If additional CD33 binding domains are developed, then therapeutic and diagnostic capabilities are enhanced, but protein structure complexity increases
Solution Approach 1:
The patent optimizes specific local regions (complementarity determining regions HCDR1-HCDR3) of the antibody variable domains to achieve high CD33 binding affinity, while keeping the overall protein structure relatively simple and modular for ease of production
Solution Approach 2:
The invention extracts and utilizes only the essential binding functionality (VH domains with specific CDRs) needed for CD33 recognition, discarding unnecessary complexity from full-length antibodies, thereby simplifying production while maintaining therapeutic efficacy
Data Source
AI summary
The invention provides antigen binding domains that bind myeloid cell surface antigen CD33 protein comprising the antigen binding domains that bind CD33, polynucleotides encoding them, vectors, host cells, methods of making and using them.