Baylor Genetics, Miraca Research Institute Explore EV Purification for Cancer-Based Applications
HOUSTON, TX (OCT. 21, 2019)
As part of a new research project, Baylor Genetics, Baylor College of Medicine (BCM), and Tokyo-based Miraca Research Institute (MRI) have begun to explore extracellular vesicles (EVs) for cancer detection and monitoring. Launching a pilot project later this month, the international group will validate MRI’s antibody reagents and prototype EV isolation system to identify potential breast and pancreatic cancer biomarkers.
According to Shashikant Kulkarni, CSO of Houston-based Baylor Genetics, the ultimate goal of the new project will be to develop a clinical test that uses EVs as part of a comprehensive method — in addition to circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) — to detect early stages of cancer in patients. Kulkarni, who is also a professor of molecular and human genetics at BCM, said his team will initially focus on EVs because it has done similar work on this sample type in the past. He also believes that genetic information in exosomes is more comprehensive and reliable than, and complementary to, cell-free DNA and CTCs.
MRI has developed a cocktail of proprietary antibody reagents that it believes can significantly improve exosome purification from liquid samples. Takuya Sakyu, an R&D manager at Baylor Genomics, noted that MRI is also developing a benchtop automated EV isolation system (Auto EVIS) that Baylor Genetics will validate during the project.
To use Auto EVIS, researchers first inject a liquid sample into a vial filled with antibody-conjugate magnetic beads, which then bind to EVs. After performing a washing step to remove proteins and other impurities, researchers can elute the EVs for downstream analysis.
On a poster that MRI plans to present later this month at a cancer conference in Boston, the team showed that Auto EVIS can process up to six liquid samples per run and produce purified EV within 75 minutes. In addition to plasma, Auto EVIS can extract EVs out of serum, urine, and saliva samples. Kulkarni noted the instrument allows researchers to “isolate exosomes that could have better readouts than ctDNA and let us look at structural variants.”
As part of the new collaboration, BCM will provide clinical breast and pancreatic cancer samples. Baylor Genetics will collect 2 microliter blood samples from 50 patients in each cancer type and use MRI’s reagents to validate the prototype purification instrument. MRI will help train Baylor Genetics’ technologists to use Auto EVIS with the cocktail of reagents to extract and purify EVs from each blood sample.
Kulkarni’s team will then perform DNA and RNA sequencing on collected EVs using a variety of downstream tools available at one of BCM’s advanced technology core labs, with the goal of identifying potential biomarkers for breast and pancreatic cancer.
“While our initial focus is in genomics and transcriptomics, where we have already been partnering with leaders at BCM, we have spoken to collaborators in the lung and breast cancer space, with the goal of potentially performing proteomics on the 100 samples,” Kulkarni said.
If the researchers collect enough actionable data in the pilot project, Kulkarni said, the team will contact BCM’s US and international precision medicine partners and hopefully launch additional clinical validation studies.
“We have outreach with healthcare systems across the whole world, including Europe, India, China, and Hong Kong, so we will have no problems collecting clinical samples,” Kulkarni said. “Depending on how much material we get from the initial group, we will use mass spectrometry or proteomics-based tools as well.”
Sakyu noted that MRI holds a patent on the antibody reagents that emphasizes the isolation efficiency and storage stability of liquid samples. He explained that the reagents can be used with universal exosome markers (including CD9 and CD63) as well as other cell surface markers.
Baylor Genetics aims to eventually develop a diagnostic and prognostic tool based on the reagents and prototype platform for both research and clinical use. The group will offer the proposed tool as a laboratory-developed test that will be commercialized through Baylor Genetics.
Kulkarni argued that the pilot project stands out from other studies pursuing EVs for cancer detection because he believes that the platform could also be used to identify other conditions, such as prenatal diseases and neurological disorders. He also sees the method as a unique approach for applying other -omics technologies that “haven’t been used for prenatal [and neurological] conditions in the clinical setting.”
“Oncology is the first pilot project, but we are excited to work with leaders at BCM in the neurology space,” Kulkarni said. In addition, they plan to explore using antibodies to collect fetal cells.