CEACAM5 Antibody Fab Fragment for Rapid Tumor Detection
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Solution Overview
Problem
Current anti-human CEACAM5 antibody Fab fragments face challenges such as attenuated binding activity due to labeling and rapid renal excretion, making them less effective for detecting hepatic metastasis within a short time frame.
Innovation Solution
Development of an anti-human CEACAM5 antibody Fab fragment with specific amino acid sequences for the heavy and light chain variable regions, combined with a labeling moiety, that maintains binding activity and accumulates in cancer lesions within 4 hours after administration, allowing for early detection of cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional anti-human CEACAM5 antibodies are used for diagnosis, then they provide high specificity for tumor cells, but they require 4-5 days to reach sufficient tumor-to-blood ratio and accumulate in the liver causing high background signal
Solution Approach 1:
The patent divides the antibody molecule into Fab fragments (antigen-binding fragments) that lack the Fc region. This segmentation reduces the molecular size and eliminates liver metabolism, enabling rapid accumulation in tumors within hours while avoiding the 4-5 day waiting period required by conventional antibodies.
Solution Approach 2:
The Fab fragments are designed as short-lived diagnostic agents that rapidly accumulate in tumors and are quickly cleared from blood through renal excretion. This short half-life in blood (compared to conventional antibodies) enables early detection within hours rather than days, reducing the time loss for diagnosis.
2Measurement precision
If conventional antibodies are used, then they provide sustained presence in blood, but they accumulate in the liver causing high background signal that prevents detection of hepatic metastasis
Solution Approach 1:
The patent extracts and removes the Fc region from the antibody molecule, retaining only the Fab fragments. This extraction eliminates the portion responsible for liver accumulation and ADCC/CDC effects, thereby reducing liver background signal while preserving tumor-targeting capability through the intact antigen-binding region.
Solution Approach 2:
The patent converts the harmful effect of Fc-mediated liver accumulation into a benefit by using Fab fragments that rely on renal excretion for clearance. This conversion transforms the accumulation pattern from liver-dominated (harmful for hepatic metastasis detection) to kidney-dominated (beneficial for reducing liver background and improving signal-to-background ratio).
3Speed
If Fab fragments are used for diagnosis, then they accumulate rapidly in tumors, but labeling reduces their binding activity
Solution Approach 1:
The patent applies labeling moieties selectively to specific regions of the Fab fragment that do not interfere with the antigen-binding site. This localized labeling approach maintains the high binding activity and tumor accumulation speed by ensuring the label is positioned in a way that preserves the integrity of the antigen-binding region.
Data Source
AI summary
Provided are an anti-human CEACAM5 antibody Fab fragment expected to be useful in the diagnosis of a cancer, particularly, the diagnosis of colorectal cancer, breast cancer, lung cancer, thyroid gland cancer or a cancer resulting from the metastasis thereof, and a diagnosis approach using a conjugate comprising the Fab fragment. The present invention provides an anti-human CEACAM5 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by amino acid positions 1 to 121 of SEQ ID NO: 2, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by amino acid positions 1 to 112 of SEQ ID NO: 4, and a conjugate comprising the Fab fragment.