Betaig-h3 Biomarker for Pancreatic Cancer Detection
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Solution Overview
Problem
Current methods for diagnosing and treating pancreatic ductal adenocarcinoma (PDAC) are inefficient due to the disease's high resistance to treatments and lack of reliable diagnostic biomarkers, leading to poor prognosis and limited patient survival, with existing treatments being invasive and ineffective.
Innovation Solution
Measuring the level of βig-h3 protein in blood samples to assess the risk of PDAC and using βig-h3 antagonists to neutralize its immunological checkpoint function, thereby enhancing CD8+ T cell anti-tumoral responses and potentially treating the disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatment approaches (surgery, radiation, chemotherapy) are used, then treatment options are available, but the prognosis is dismal with only 20% of patients alive one year after diagnosis due to high drug resistance and inefficient treatment
Solution Approach 1:
The patent introduces βig-h3 as an intermediary biomarker that mediates between the tumor stroma and the immune system. By detecting βig-h3 levels in blood samples, the invention enables non-invasive monitoring of tumor stroma composition, which correlates with treatment response and patient prognosis, thereby improving treatment effectiveness without requiring invasive procedures
Solution Approach 2:
The invention changes the monitoring parameter from invasive tissue biopsy to non-invasive blood sample analysis. By measuring βig-h3 protein levels in blood, the system provides a reliable parameter that reflects tumor stroma characteristics and predicts treatment response, enabling better prognostic assessment without compromising patient safety
2Measurement precision
If invasive intra-tumor biopsy is performed for diagnosis, then direct tumor sampling is achieved, but the procedure is invasive and complex
Solution Approach 1:
The patent uses βig-h3 as an intermediary marker that bridges the gap between tumor stroma and blood circulation. This mediator allows the system to indirectly detect tumor presence and characteristics through blood samples, eliminating the need for direct invasive biopsy while maintaining diagnostic accuracy
Solution Approach 2:
The invention replaces the mechanical invasive biopsy procedure with a biochemical detection method. Instead of physically removing tumor tissue, the system uses blood sample analysis to detect βig-h3 protein levels, substituting a less invasive biochemical measurement for a mechanically invasive procedure
3Ease of operation
If blood sample analysis is used for early detection, then non-invasive monitoring is achieved, but reliable diagnostic biomarkers are lacking
Solution Approach 1:
The patent creates a reliable copy of tumor stroma characteristics through the βig-h3 protein marker. This marker serves as a faithful replica of the tumor microenvironment state, allowing blood-based detection to accurately reflect tumor presence and progression without requiring direct tissue sampling
Solution Approach 2:
The invention uses readily available blood samples as a disposable, easily obtainable medium for detection. Instead of requiring complex, invasive procedures, the system utilizes simple blood tests that can be performed repeatedly and easily, making monitoring accessible and practical for clinical use
Data Source
AI summary
The present invention relates to a non invasive diagnostic method of pancreatic ductal adenocarcinoma (PDAC) in a subject said method comprising the step of measuring the level of βig-h3 protein in a blood sample wherein the serum level of βig-h3 is positively correlated with the risk of having a PDAC. By following studies on 2 distinct cohorts of 20 and 104 of PDAC patients, and on PDAC mouse model, the inventors show that βig-h3 can be directly detected in the blood sample and βig-h3 is expressed very early in tumorigenesis in pancreatic neoplastic lesions. The present invention also relates to antagonist of βig-h3 protein, for use in the treatment of PDAC. The inventors found that βig-h3 bind directly on CD8+ T cells by reducing their activation and cytotoxic properties. Furthermore, the use of neutralizing βig-h3 antibodies in PDAC mouse model, reduced tumor growth by enhancing CD8+ T cell anti-tumoral response. Thus, neutralizing βig-h3 which acts as a novel immunological check-point target in PDAC therefore allows to restore beneficial anti-tumor immunity in PDAC.