This article is more than 5 years old. Information may no longer be current.
‘Platelet decoys’ may lower blood clot risk, prevent cancer metastasis
Click Here to Manage Email Alerts
A novel antiplatelet therapy showed potential in reducing blood clot risk and preventing cancer metastasis, according to preclinical research findings published in Science Translational Medicine.
The therapy involves modification of human platelets to create “decoys” that can bind to certain cells but will not carry out other normal platelet functions, such as those associated with clotting, according to a press release.
“The reversibility and immediate onset of action are major advantages of our ‘platelet decoys,’ and we envision them to be useful as a potential antimetastatic therapy and periprocedural antithrombotic agent,” Anne-Laure Papa, PhD, assistant professor of biomedical engineering at The George Washington University, said in the release. “The therapy could prevent clotting in high-risk patients just before they undergo surgery, or be given to patients [with cancer] alongside chemotherapy to prevent existing tumors from spreading.”
HemOnc Today spoke with Papa about what prompted this research, how the platelet decoys function and what she hopes clinicians will take away from the findings.
Question: What prompted this research?
Answer: I worked with two physicians who were interested in the effect of antiplatelet therapy to boost drug delivery to tumors in an animal model. The encouraging data from this approach prompted my interest in trying to design a therapeutic that could intercept circulating tumor cells in the bloodstream, before they create metastases. The association of platelets, cancer progression and thrombosis has been well-established. We know that platelets bind to circulating tumor cells in the bloodstream to help them navigate this harsh environment and survive to form new metastatic niches. We wanted to leverage this platelet support to tumor cells as a means to target them while they are susceptible in the circulation. I was a postdoctoral fellow at Harvard University’s Wyss Institute in the laboratory of Donald E. Ingber, MD, when the research was conducted.
Q: What is the rationale for why this technology may work?
A: Designing inert platelets capable of binding to tumor cells, while not providing them with vital survival support, was the crux of our technology. The goal was to compete with natural platelets in the bloodstream to abate their supportive effect. The circulation provides an opportunity where the tumor cells are accessible and can be targeted. Our hypothesis was that platelet decoys would occupy binding sites on cancer cells, preventing platelets from accessing and supporting the process of metastatic dissemination.
Q: How did you conduct the study?
A: First we checked to see whether these modified platelets still bind to cancer cells. About 40% of the main receptor implicated in the interaction between the cells and platelets is lost during the process of these platelet decoys. Still, we were able to show that these platelets bind to cancer cells. We then collaborated with other researchers and quickly reversed the effects of the decoys on normal platelets by introducing fresh platelets into the blood.
Q: What did you find?
A: Platelet decoys inhibited aggregation and adhesion of platelets on thrombogenic surfaces in vitro, which could be immediately reversed by the addition of normal platelets. The platelet decoys also interfered with platelet-mediated human breast cancer cell aggregation, and their presence decreased cancer cell arrest and extravasation in a microfluidic human microvasculature on a chip.
In addition, simultaneous injection of the platelet decoys with tumor cells inhibited metastatic tumor growth, suggesting that platelet decoys might represent an effective strategy for obtaining antithrombotic and antimetastatic effects.
Q: What is next for research on this?
A: We need to assess the circulation time in comparison with platelets. This is the first treatment platform that is drug-free and it may have an effect on thrombosis as well. We also hope to study whether platelet decoys can be used as drug transporters to target platelet-related conditions. We may find an additional synergistic effect on preventing cancer metastasis. There is still a lot of work to accomplish. – by Jennifer Southall
References:
Papa AL, et al. Sci Trans Med. 2019; doi:10.1126/scitranslmed.aau5898.
Pandey A, et al. Nanotechnology. 2014;doi:10.1088/0957-4484/25/44/445101.
For more information:
Anne-Laure Papa, PhD, can be reached at The George Washington University Science and Engineering Hall, Office 5665, 800 22nd St. NW, Washington, DC 20052; email: alpapa@gwu.edu.
Disclosure: Papa reports a patent application, “Platelet decoys and use thereof.”