all the information, none of the junk | biotech • healthcare • life sciences

MGH-Veridex Device Enters Challenging Arena in Tumor Cell Testing

Xconomy Boston — 

Mehmet Toner wants cancer doctors to be able to see what he can see.

Most oncologists rely on imaging tools like CT scans, and perhaps only a single biopsy, to learn what they can about patients’ tumors and the biological traits of their cancer cells. Toner, a biomedical engineering specialist, says he can track the evolving nature of an individual’s cancer cells in real time—as they mutate or respond to treatment—by capturing the tumor cells that have broken loose to circulate in the patient’s blood.

Toner’s work with colleagues at the Massachusetts General Hospital Center for Engineering in Medicine recently stirred up renewed interest in the potential of circulating tumor cells for a range of uses. They could be a future focus of routine diagnostic tests, a guide to the development of personalized cancer drugs, and a research tool that could unveil the mysteries of metastasis.

Toner’s window on cancer comes from a microfluidics-based system called the CTC-iChip that he and his team developed at Massachusetts General in a three-way collaboration with Veridex of Raritan, NJ, a diagnostics division of Johnson & Johnson, and Veridex’s affiliate Janssen Research & Development. The device plucks out the very few circulating tumor cells, or CTCs, from among the billions of other cells floating in the blood.

Those tumor cells could give doctors and clinical trial investigators a series of status updates over the course of a patient’s diagnosis and treatment, Toner says. CTC testing could provide information about the changing genetics of tumor cells to steer the use of cancer therapies that are targeted at specific mutations. And this could be done without additional invasive biopsies, Toner says.

“Doing multiple solid tumor biopsies is very difficult,” says Toner, director of the BioMicroElectroMechanical Systems Resource Center at Massachusetts General’s Center for Engineering in Medicine. “This will be what we call a liquid biopsy.”

The theoretical promise of CTC testing has captivated researchers and science buffs as well as profit-seeking venture capital firms. The CTC-iChip drew a flurry of media coverage after Toner’s team published early study results on the system in Science Translational Medicine during the annual meeting of the American Association for Cancer Research (AACR) that ran through April 10.

But as the AACR meeting wrapped up, a prominent venture firm partner who had invested in a CTC testing startup, Bruce Booth of Cambridge, MA-based Atlas Venture, said in a rueful blog post that the technology may not be ripe for commercial success for another five to 10 years. Booth said his firm’s portfolio company, Waltham, MA-based On-Q-ity, is folding up and selling the last of its intellectual property assets this month—his first total write-off in nine years in the venture capital business.

Booth still thinks he was right about the eventual promise of CTC testing—but not the market timing. It would have taken On-Q-ity years of expensive research to prove that a promising benchtop assay could be a marketable product used by doctors in clinical practice, he concluded.

“The capture and characterization of CTCs will be an important part of oncology care in the next decade. This I’m fairly sure of, and all the news from AACR earlier this week about ‘liquid biopsies‘ supports this premise,” Booth wrote. “But the reality is it’s a research-stage story right now, and in diagnostics (unlike drugs) it’s hard to get paid for research-stage stories.”

Mehmet Toner, however, is hoping that doctors will have his team’s CTC-iChip in their hands before very many years pass. His most fervent goal is to see the CTC test used as a sentinel assay to detect cancer very early, before tumor masses appear in imaging tests—by which point it may be too late for a cure. The device was developed in a joint effort with Veridex, which currently has the only FDA-approved in vitro diagnostic assay for CTC capture and counting. Veridex has the right to acquire the CTC-iChip and commercialize it.

“They really know the territory,” Toner says. “They’re the right partner.”

Veridex’s studies indicate that its CTC testing system already on the market, CellSearch, can help doctors predict the long-term survival prospects of patients in three major cancer types by tracking the total counts of circulating tumor cells at intervals before and after treatment.

The company launched its collaboration with the Massachusetts General team in January of 2011 to go further than merely enumerating the captured tumor cells. Greater diagnostic power could come from analyzing the tumor cells in blood in a search for biomarkers that might become drug targets or guides to treatment decisions.

Toner says the latest version of his team’s CTC testing system isolates a broader range of tumor cell types, revealing the heterogeneity of the disease’s molecular traits within individual patients. The Massachusetts General device does this with a tweak that differentiates it from the Veridex system.

The Toner team had started out with a method like Veridex’s for separating the tumor cells from other blood-borne cells. Veridex uses antibodies that selectively stick to a molecule on the surface of CTCs, such as the protein called EpCAM . Once stuck, the CTCs flow into different microfluidic channels from the other cells in the blood. But some tumor cells don’t bear the EpCAM molecule, so they may evade capture.

The third-generation CTC-iChip can work in a different mode. Instead of using antibodies to pluck out the tumor cells, it pulls away the non-tumor cells—red blood cells and white blood cells—using various means such as antibodies to those non-tumor cells, magnetic beads, and filtering by cell size. This subtractive process leaves only the tumor cells —including those without EpCAM or any other surface marker a Veridex-like system might have fished for with antibody “hooks.”

Those tumor cells may uncover a fuller range of malignant mutations in a patient’s body than a biopsy of a single tumor site. The single rare cells, once captured, can then be subjected to further tests, such as gene expression studies or assays for drug resistance.

Veridex called the CTC-iChip its “next-generation circulating tumor cell (CTC) technology” in a written statement celebrating the Toner team’s publication in Science Translational Medicine. Veridex said the device “offers enhanced specificity and sensitivity and enables more extensive characterization of captured cells,” as well as the ability to process large blood volumes “with high throughput and efficiency.”

But the timeline for commercial development of the CTC-iChip may be uncertain, or lengthy. Veridex didn’t respond to Xconomy’s inquiries about the development plan going forward, and about current revenues for its marketed system, CellSearch.

Mike Stocum, president and founder of the consulting firm Personalized Medicine Partners, says the primary market for CTC testing systems at this point is among research units at universities, government agencies such as the NIH, and drug companies. But CTC testing products may never pay off the money poured into their development until they break through into common use by practicing doctors, Stocum says.

“In order to get a return on investment, you’ve got to get routine clinical adoption,” he says. It might take revenues of $100 million or more per year, for a number of years, to pay off the development costs, Stocum says.

Stocum was hired in late 2011 as On-Q-ity’s CEO, when the startup was trying to find a partner and a path forward. During the year he held the executive post, one of his priorities was to use the On-Q-ity system to analyze patients’ tumor cells and their health outcomes, and try to demonstrate that it could help doctors make decisions. But the small company ran out of funds to do those clinical studies.

CTC testing may take off in the commercial mainstream once a study emerges showing that it can make a big difference in treatment plans for a major cancer indication, Stocum says. For example, he says, a researcher is now testing CTCs to see if they can distinguish between the prostate cancers that may not cause problems for years and the aggressive cases of the disease that should be treated immediately.

“That would take us a long way,” Stocum says.

Booth, who used his blog to share a generous analysis of the lessons he learned by investing in On-Q-ity, said CTC testing must overcome the hurdles commonly faced in all diagnostics development.

“Diagnostics aren’t for the faint of heart and are a much tougher place to make returns today than other life science subsectors,” Booth wrote. “Despite the frothy commentary about personalized medicine and the dawn of diagnostics, it’s a very tough business that faces many of the risks and costs of drug R&D but without the upside. It’s often not less capital intensive than therapeutics, faces similar ‘academic validation‘ concerns, is confronted by larger reimbursement and regulatory uncertainties, has commodity-oriented high volume, low price demands, and typically needs to get to commercialization before a material exit outcome. All these things add up for a challenging investment sector.”