Exosomes and real life
GARDNER, Mass.—New England Peptide (NEP) and the Atlantic Cancer Research Institute (ACRI) have jointly submitted a patent application for cancer-related peptide reagents which the companies believe have the potential to deliver breakthroughs in cancer diagnostics and more individualized therapies for cancer patients.
The patent application's principal claims the series of peptide reagents is capable of capturing exosomes and/or microvesicles from cell culture media and various tissue fluids, and that the captured materials are primarily and specifically oriented towards any type of cancer.
"The concepts of enabling discovery in exosome research and understanding the need to expedite cancer diagnoses and improve accuracy of treatments are the main tenets of the patent," says Dr. Steve Griffiths, researcher at Moncton, New Brunswick-based ACRI, and co-inventor of the new peptides. "Existing methods give comparatively lower yields and thus present missed opportunities for detection and characterization."
One of the hallmarks of cancer cells is their high propensity to "bud off" their cellular material into small particles called microvesicles and exosomes. These particles carry a variety of information about the parent cancer cell that recently has become a primary focus of research. Early findings from cell cultures grown in the lab indicate their potential, but to maximize the overall benefit, scientists need to use cells from "real-life" samples.
"Real-life samples," in this case, refers to easily collected samples such as blood or urine, states Scott Lewis, co-inventor and director of NEP's Antibody Division. The currently accepted method for the collection and testing of potential cancerous material—the biopsy of detected tumors—is invasive, expensive and, because in many cases tumors are not even looked for until the patient is quite ill, too late to be effective, he notes.
On the other hand, the collection and subsequent testing of blood or urine samples is far easier and often already done on a yearly basis.
"Because of the comparative difference in ease and practicality between the two methods, the potential of catching relevant data at much earlier stages would be greatly increased," Lewis says. "The mRNA, miRNA and protein information found in microvesicles and exosomes thus far has already revealed known cancer biomarkers. Further research enabled by these reagents will be extremely useful in creating profiles of specific cancer types, as well as providing insight into how and why some cancers progress into being lethal and others do not."
The idea of using exosomes as a potential source of molecules of diagnostic, prognostic and theranostic interest has been generating steam ever since they were first discovered to contain known biomarkers for cancer. The problem with doing this on a widespread basis is the difficulty in collecting exosomes from whatever biological tissue is being used, since they are typically a very small part of the total material present in any sample.
"The current accepted method for exosome purification—ultracentrifugation—involves spinning a sample at very high speeds (a centrifugal force of 100,000g) to concentrate the exosomes into a pellet at the bottom of a test tube," notes Griffiths.
However, because of the limited number of labs with machines capable of such high speeds—and the popularity of such machines in these facilities—ultracentrifugation can be a major bottleneck in exosome analysis, he notes. Furthermore, without direct access to an ultracentrifuge, renting time at a facility can be a significant expense.
"Since our reagents do not require ultracentrifugation, the time and expense related to this as an issue has been removed," he states.
"Adding these two advantages together, one can easily envision the advent of personalized testing," ACRI's Griffiths adds.
His vision is that each patient would be examined for indicators of cancer of a specific threat (including severity and type) and according to the results—rather than gambling on broad-spectrum approaches of treatment that may be both inefficient and at times severely debilitating—a treatment plan would be tailored to their exact needs.
NEP's Lewis agrees: "This would give untold cumulative benefit to insurance companies, healthcare professionals and patients alike," he observes.
Moving forward, ACRI will continue to refine the reagents through its research programs and at the same time identify new applications for the derived products. NEP will be responsible for manufacturing and commercialization.