Recombinant sCD38 Neutralizes Anti-CD38 Antibodies
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Solution Overview
Problem
Current methods for addressing interference from anti-CD38 antibodies, such as Darzalex, in blood compatibility testing are either costly, damage blood group antigens, or fail to detect clinically relevant irregular antibodies, necessitating a more effective and cost-efficient solution for neutralizing these antibodies without disrupting epitopes on red blood cells.
Innovation Solution
A recombinant soluble form of the CD38 extracellular domain (sCD38) is expressed using eukaryotic or prokaryotic systems, fused with oligomerization tags like the immunoglobulin Fc region and polyHis domain, allowing for high concentration and efficient neutralization of anti-CD38 antibodies, thereby facilitating accurate blood compatibility testing without damaging blood group antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods are used to address interference from anti-CD38 antibodies, then neutralization is achieved, but the methods are costly or damage blood group antigens
Solution Approach 1:
The patent uses a recombinant soluble CD38 extracellular domain (sCD38) as an intermediary substance to neutralize anti-CD38 antibodies. This mediator binds specifically to the therapeutic antibodies, preventing them from interacting with CD38 on red blood cells, thereby eliminating interference without damaging blood group antigens.
Solution Approach 2:
The invention creates a soluble copy of the CD38 extracellular domain that can be produced recombinantly in large quantities. This copy (sCD38) mimics the native CD38 antigen structure and function, allowing it to effectively compete for antibody binding without requiring the complex cellular context of the original antigen.
2Object-affected harmful factors
If current methods are used to neutralize anti-CD38 antibodies, then interference is reduced, but detection of irregular antibodies is compromised
Solution Approach 1:
The sCD38 is applied in a preliminary step before the actual blood compatibility testing. This preliminary neutralization action removes the interfering anti-CD38 antibodies from the sample, allowing subsequent testing procedures to accurately detect irregular antibodies without false interference signals.
Solution Approach 2:
The invention effectively extracts or removes the interfering anti-CD38 antibodies from the test system by introducing sCD38 that selectively binds these antibodies. This extraction of the harmful element allows the remaining system to function normally for detecting clinically relevant irregular antibodies.
3Reliability
If recombinant sCD38 is used for neutralization, then antibody binding is blocked, but production cost and complexity increase
Solution Approach 1:
The invention segments the CD38 protein by using only the extracellular domain (amino acids 1-290) rather than the full transmembrane protein. This segmentation creates a smaller, soluble fragment that is easier to produce recombinantly while retaining all necessary epitopes for antibody binding and neutralization functionality.
Solution Approach 2:
The patent employs a disposable oligomerization tag (10xHistidine tag) that facilitates purification through metal affinity chromatography using inexpensive nickel or cobalt resins. This approach eliminates the need for complex, expensive purification systems while enabling efficient production of the recombinant sCD38.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The recombinant sCD38 effectively neutralizes anti-CD38 antibodies with high efficacy (>70% to 100%), allowing for the detection of irregular antibodies and ensuring compatible blood transfusions, while maintaining the stability and functionality of blood group antigens.
Implementation Method 1
a recombinant soluble form of an extracellular domain of CD38 and/or a fragment thereof that interferes with a binding activity of an anti-CD38 antibody
Data Source
AI summary
A composition that binds to an anti-CD38 antibody includes a specific sequence of a recombinant soluble form of an extracellular domain of CD38 and/or a fragment thereof that interferes with binding activity of the anti-CD38 antibody. The composition can be included in a kit for bio-monitoring research and diagnostic assays. The composition can be used to neutralize an anti-CD38 antibody in a sample and/or to select a suitable red blood cell unit for a patient treated with anti-CD38 antibodies.