Neo-Epitope Biomarker Assay for Stroma-Rich Tumor Detection
Solution Overview
Problem
Current biomarkers are inadequate for non-invasively identifying patients with cancers characterized by a stroma- and cancer-associated fibroblast-rich tumor microenvironment, such as pancreatic cancer, and for predicting response and survival outcomes for immune checkpoint inhibitor therapy.
Innovation Solution
Development of an enzyme-linked immunosorbent assay (ELISA) targeting the C-terminus neo-epitope generated by enzymatic cleavage of the N-terminal pro-peptide of the α1-chain of type XI collagen at A′511↓, using a monoclonal antibody that specifically binds to the C-terminus amino acid sequence DGSKGPTISA, for detecting and quantifying the biomarker in biofluids to assess disease severity and prognosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current biomarkers are used for non-invasive detection, then detection can be performed minimally invasively, but the ability to identify patients with stroma-rich tumors and predict immune checkpoint inhibitor response is insufficient
Solution Approach 1:
The invention changes the biomarker parameter from general collagen markers (PRO-C3, PRO-C1) to a specific neo-epitope marker (PRO-C11-511) generated by cleavage at position 511 of the N-terminal pro-peptide of the α1-chain of type XI collagen. This parameter change enables the assay to specifically detect fibroblast-derived collagen in stroma-rich tumors and predict immune checkpoint inhibitor response with high accuracy
Solution Approach 2:
The invention extracts and targets a specific neo-epitope region (C-terminus amino acid sequence DGSKGPTISA) generated by enzymatic cleavage of the pro-peptide. By focusing on this specific extracted region rather than the entire collagen molecule, the assay achieves high specificity for fibroblast-derived collagen and improved predictive capability for ICI therapy response
2Loss of information
If existing collagen biomarkers are used, then some information about collagen turnover can be obtained, but specific information about fibroblast-derived collagen and tumor stroma activity is lost
Solution Approach 1:
The invention applies local quality by targeting a specific local region (the C-terminus neo-epitope at position 511) of the collagen pro-peptide that is uniquely generated by fibroblast-derived collagen processing. This localized targeting provides specific information about fibroblast activity in the tumor stroma, distinguishing it from other collagen sources
Solution Approach 2:
The invention uses a monoclonal antibody as an intermediary that specifically recognizes the neo-epitope sequence DGSKGPTISA. This antibody mediator enables selective detection of the cleaved pro-peptide fragment, translating the biological information about fibroblast collagen processing into a measurable signal with high specificity
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 ELISA assay demonstrates prognostic value in patients with pancreatic cancer, chronic pancreatitis, and metastatic melanoma, providing a predictive marker for overall survival and treatment response, with high specificity and sensitivity in clinical evaluations.
Implementation Method 1
using a monoclonal antibody that specifically binds to the C-terminus amino acid sequence DGSKGPTISA, for detecting and quantifying the biomarker in biofluids
Implementation Method 2
Development of an enzyme-linked immunosorbent assay (ELISA) targeting the C-terminus neo-epitope generated by enzymatic cleavage
Implementation Method 3
enzymatic cleavage of the N-terminal pro-peptide of the α1-chain of type XI collagen at A′511↓
Data Source
AI summary
Disclosed herein are monoclonal antibodies that specifically recognise and bind to a C-terminus of a peptide that is the C-terminus neo-epitope formed on cleavage of the N-terminal pro-peptide of the α1-chain of type XI collagen at A′511↓, and immunoassay methods and kits using and containing the antibodies. The immunoassay methods may be used for detecting and/or monitoring and/or assessing the severity or prognosis of diseases, such as, but not limited to, cancer.