Antibodies targeting autonomously active B-cell receptors
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Solution Overview
Problem
Current diagnostic and therapeutic approaches for malignant B-cell neoplasias, such as leukemia, are limited by non-specific antibody binding, leading to false positives and significant side effects due to the inability to selectively target autonomously active B-cell receptors, which are characteristic of tumor cells but not healthy cells.
Innovation Solution
Development of antibodies and functional fragments that specifically bind to autonomously active B-cell receptors by using genetically modified cells in a native and activated state, particularly pro-/pre-B cells, to enable targeted diagnosis and therapy with reduced side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional antibodies against BCR are used for diagnostic purposes, then broad-spectrum detection is achieved, but false positive results occur due to cross-reactions with other receptors or epitopes
Solution Approach 1:
The patent segments the BCR detection approach by identifying and targeting specific epitope regions (such as the VH3 family variable domains) that are characteristic of malignant B-cell receptors. Instead of using a single broad-spectrum antibody, the invention divides the detection strategy into multiple antibodies that each recognize specific epitopes, thereby maintaining versatility while improving precision by avoiding cross-reactions with non-target receptors
Solution Approach 2:
The patent applies local quality by designing antibodies that recognize specific local regions (epitopes) of the BCR structure, particularly the variable domains of heavy chains. This localized targeting approach allows the antibodies to distinguish between malignant and benign B-cells by recognizing epitopes that are specifically altered or overexpressed in malignant cells, thereby improving diagnostic accuracy without sacrificing the ability to detect various B-cell malignancies
2Object-generated harmful factors
If chemotherapy is used to treat leukaemias, then tumor cell destruction is achieved, but healthy immune system cells are damaged causing severe side effects
Solution Approach 1:
The patent employs monoclonal antibodies as intermediary agents that specifically bind to antigens expressed on the surface of malignant B-cells. These antibodies serve as mediators between the diagnostic/therapeutic system and the target cells, enabling selective identification and treatment of tumor cells through mechanisms such as flow cytometry detection and targeted therapy, thereby sparing healthy immune cells from the collateral damage caused by conventional chemotherapy
Solution Approach 2:
The patent utilizes parameter changes in the form of fluorescently labeled antibodies and detection systems. By changing the detection parameter from general cell morphology to specific antigen-antibody binding events detected through fluorescence, the system achieves high specificity for malignant cells. This parameter change enables differentiation between healthy and malignant cells based on the presence of specific surface markers, allowing for targeted treatment that minimizes damage to healthy cells
3Ease of manufacture
If established cell lines are used for antibody testing, then easy cultivation is achieved, but cross-reactions with other receptors occur reducing antibody specificity
Solution Approach 1:
The patent uses copying by creating recombinant forms of the target antigens and expressing them in suitable cell systems. By copying the specific epitope structures of interest and presenting them on the surface of test cells, the invention enables screening of antibodies against defined, controlled targets. This approach allows for rigorous specificity testing while maintaining the practical advantages of using established cell lines, as the recombinant antigen expression can be precisely controlled to avoid cross-reactivity issues
Data Source
AI summary
The present invention relates to the field of production, identification and selection of biological binding molecules such as antibodies or fragments thereof, as well as to diagnostic procedures using them in the diagnosis of cancers, in particular malignant B-cell neoplasia. The binding molecules are able to selectively bind to autonomously active or autonomously activated B-cell receptors, the autonomously active or autonomously activated B-cell receptors being characterized by the presence of structural domains to which the binding molecule selectively binds and which are responsible for the autonomously active or autonomously activated state of the B-cell receptors.