Xin Ye, Director of product development at Sanmed Biotech LTD
I had the pleasure of speaking to Xin Ye, an Experienced Senior Project Scientist and Director of product development at Sanmed Biotech, focused on developing Circulating Tumor Cell (CTC) capture and detection technologies. Xin attained a Ph.D. in Biochemistry from the University of Illinois at Urbana-Champaign. He joined Sanmed in 2017 as a senior scientist and later fulfilled the role of Head of R&D.
The liquid biopsy market is rapidly evolving in China. Can you share some insights on driving forces that facilitate and hinder the introduction of LB into a clinical routine in the Chinese market?
The analysis of tumor cells or tumor-related matters (e.g. cell-free DNA and exosome) obtained from blood or other body fluids offers a broad range of opportunities in the field of oncology. The ideas of noninvasively portraying the entire disease at the cellular and molecular level and providing real-time comprehensive tumor information on cancer evolution, therapeutic strategies, and resistance mechanisms are attractive to both researchers and physicians. The potential clinical application areas include early detection of cancer, recurrence risk assessment, drug efficacy monitoring also propel many institutes and industrial companies to invest in liquid biopsy technologies.
” .. aiming to extrapolate the use of the different circulating molecules into the “real world” in clinics .. “
Nonetheless, solid biopsies are the current standard of care in clinical cancer management with unquestionable utilities in tumor histology, biomarker subtyping, and molecular profiling for treatment planning and prognostic. The detection and characterization of circulating tumor materials in the early or advanced setting present much more difficulties due to their low amounts in the biofluids from the patients. The consensus among the physicians is that more research still needs to be performed in the standardization of sample extraction procedures, circulating-tumor material isolation, and the very diverse methodologies employed, aiming to extrapolate the use of the different circulating molecules into the “real world” in clinics.
It is undeniable that liquid biopsies show great promise based on the data from many studies. However, its clinical utility is still to be fully established and requires performing large-scale multicentre clinical studies. On top of that, the regulatory authorities, not only in China, still hesitate to approve liquid biopsy products due to the lack of clear methodological standards and biological evidence that also hamper the implementation of LB into clinical routine practice.
” CTCs contain genetic abnormalities similar to those in primary tumors using the combination of immunohistochemistry and fluorescence in-situ hybridization (FISH) “
In recent years, researchers have attempted to isolate tumor cells migrated from the primary tumor or metastases into the blood or other body fluids. Such circulating tumor cells (CTC) could be released at any stage of the tumorigenesis, even from a localized tumor. Capture or isolation of CTCs from peripheral blood use a variety of techniques include immunomagnetic capture of EpCAM-positive cells, filtration or density gradient separation based on cell physical properties. However, usually very few CTCs, which were traditionally identified as Cytokaritin-positive and CD45-negative by immunofluorescence staining, are recovered from these techniques.
Previous studies have reported that CTCs in the bloodstream contain genetic abnormalities similar to those in primary tumors using the combination of immunohistochemistry and fluorescence in-situ hybridization (FISH). Based on Katz, et al results of adenocarcinomas and squamous cell carcinomas using CGH arrays, four chromosomal loci were selected and verified that cells with these cytogenetic abnormalities were detected in lung cancer patient specimens by FISH. In our recent studies, using a label-free method to enumerate circulating genetically abnormal cells (CACs) by four-color FISH, early-stage NSCLC patients had significantly higher numbers of CACs than did benign and healthy controls. The presence of CACs above a certain threshold could be used as a bio-indicator for lung cancer risk stratifications, especially for populations with indeterminate pulmonary nodules.
” The use of a FISH assay with no epithelial capture component to detect CAC is unique and attractive as it is not relying on specific antigenic expressions “
You’ve recently published a paper on the diagnosis of Non-Small Cell Lung Cancer via Liquid Biopsy; there you’ve presented a unique approach leveraging Fluorescence-in-situ hybridization for the characterization of CACs. What are the highlights of this methodology and how can it be integrated into the clinical routine of LC patients?
The use of a FISH assay with no epithelial capture component to detect CAC is unique and attractive as it is not relying on specific antigenic expressions, which are highly heterogeneous in tumor cells, and may reveal more CACs that could be limited by an antigenic assay for epithelial differentiation. The FISH assay could characterize losses and gains of certain chromosomal regions regardless of the lineage of these cells and could simultaneously detect multiple DNA probes at the single-cell level. Integrating the FISH assay with BioView’s high-throughput automated fluorescent scanning solution, enable us to interrogate multicolor fluorescent signals for different genes on a per-cell basis and precisely quantify CACs population surrounded by up to several hundred million lymphocytes and neutrophils per ml of peripheral blood.
Beyond the liquid biopsy biomarker, we crossed the “one analyte” barrier focusing on the multi-omics solution by using Sanmed’s proprietary CT artificial intelligence analysis to generate pulmonary nodule malignancy prediction. Using machine learning-based modeling and large patient data from the multicenter clinical studies, the FISH assay, in conjunction with the AI interpretation of the lung nodule plays a synergistic role and could achieve early lung cancer detection close to 90% accuracy. We believe that our methodologies could be seamlessly integrated with the early lung cancer screening and routine diagnostic workflow and become an important tool to shift the current clinical landscape.
