EpCAM Binding Proteins With Conditional CAR Targeting
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Solution Overview
Problem
There is a need for more treatment options for conditions associated with abnormal expression of EpCAM, particularly in cancers, to allow for personalized therapeutic choices with better side effect profiles.
Innovation Solution
Development of novel EpCAM binding domains and multispecific proteins, including chimeric antigen receptors (CARs) and conditionally active CARs (ProCARs), which incorporate complementarity determining regions (CDRs) and cleavable linkers to selectively target EpCAM-positive cells, combined with CD3 and serum albumin binding domains for enhanced therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-EpCAM antibodies are used for cancer treatment, then EpCAM-positive tumor cells can be targeted, but the therapeutic efficacy is limited and side effects are significant
Solution Approach 1:
The patent divides the therapeutic approach into multiple specific components: different antibody formats (full IgG, Fab fragments, scFv), various conjugation strategies (toxin, radionuclide, cytokine), and multiple EpCAM-specific antibodies with different characteristics. This segmentation allows selection of the most appropriate therapy for each patient's specific condition, improving efficacy while managing side effects through personalized treatment selection.
Solution Approach 2:
The patent employs parameter changes by modifying antibody properties such as binding affinity (Kd values ranging from nM to pM), molecular format (size, structure), and conjugation parameters (toxin type, radionuclide selection). These parameter variations enable optimization of therapeutic index by adjusting potency, specificity, and toxicity profiles to match individual patient needs and tumor characteristics.
2Adaptability or versatility
If more treatment options are developed for EpCAM-positive cancers, then personalized therapeutic choices improve, but the complexity of treatment selection and development increases
Solution Approach 1:
The patent creates a universal platform for EpCAM-targeted therapy that encompasses multiple antibody formats, conjugation types, and delivery mechanisms all targeting the same antigen. This multi-functional approach allows a single target (EpCAM) to be addressed through diverse therapeutic modalities, providing personalized options without requiring development of entirely separate targeting systems for each treatment type.
Solution Approach 2:
The patent performs preliminary characterization and classification of multiple EpCAM antibodies and therapeutic conjugates with defined binding affinities, specificities, and toxicity profiles. This advance preparation creates a pre-evaluated library of treatment options with known parameters, simplifying the clinical decision-making process by providing physicians with pre-characterized agents rather than requiring de novo evaluation of each treatment option.
Data Source
AI summary
Provided herein are EpCAM binding proteins, pharmaceutical compositions comprising such proteins or fragments thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such EpCAM binding proteins. Also disclosed are methods of using the disclosed EpCAM binding proteins in the prevention, and/or treatment diseases, conditions and disorders.