NEW YORK (360Dx) – The last year has seen a wave of excitement and investment into companies and research groups hoping to launch early cancer detection and screening tests that sift the blood for small fragments of cancer-associated DNA.
But considering the costs of genomic technologies, there is also much skepticism that circulating DNA is the best target for a test or series of tests to be applied to a broad population.
With the technological details behind projects by firms like Grail and Freenome still closely guarded, the diagnostics industry has seen other players emerge that believe that proteins and immune cells could offer sensitive cancer screening at a more appropriate price than DNA-based technologies.
One new entrant to the race for early detection, ITUS, is developing a test through its subsidiary Anixa Diagnostics, which is based on quantitation of a subtype of immune cells called myeloid-derived suppressor cells (MDSCs), which play a role in the tumor microenvironment.
This week, the company announced that the United States Patent and Trademark Office has issued it a patent — number 9,739,783 — covering certain aspects of its computational and technological approach.
The test is not a straightforward detection or quantification of MDSCs. It involves the use of a pattern-recognition via artificial intelligence, or neural network technology, which the company has trained to analyze data generated by flow cytometry, distinguish between the immunological responses of cancer patients and healthy patients using up to 13 quantitative parameters.
The firm first began promoting the technology early last year, and began to share early validation data last winter. ITUS claims that it has been able to reach a sensitivity and specificity of 92 percent with the MDSC approach it calls CCheck, as calculated from a study of 88 patient samples, including 54 samples from patients with multiple types and severities of cancer, and 34 healthy patients.
And although ITUS has yet to publish any of this data in the peer-reviewed literature, CEO Amit Kumar said that it is talking to potential development partners, with which it hopes to collect enough data to begin discussions with the US Food and Drug Administration by the middle of next year.
The commercial strategy will be to pick a single cancer type to focus its first product on — most likely prostate or breast cancer — and then work on additional assays after that, Kumar explained. Overall, the firm has looked at 15 types of cancer, all of which showed promise for MDSC-based early detection.
ITUS is not alone in its interest in MDSCs. Researchers at the University of Southern California, for example, have also patented a method for quantitating MDSCs as a way of monitoring cancer patients' response to therapy and predicting their disease course or malignancy risk.
MDSCs are corrupted myeloid cells, a type of immune cell that travels to the site of a tumor as part of the body's immune response to cancer. However, tumors develop ways to corrupt the formation of normal myeloid cells, turning them into immune suppressors, known as MDSCs.
USC pathology professor Alan Epstein said in an interview that MDSC's role in cancer immune evasion is well established. The ability to detect and quantitate these cells using flow cytometry has also been demonstrated by his own group, so that aspect of ITUS' approach appears valid, he added.
For their own part, the USC team is developing assays not for early cancer detection or screening in broad populations, but to serve specific niche needs, like determining whether patients who present with nodules or other precancerous symptoms, are at risk of progressing to malignant cancer or can avoid unnecessary treatment for what is a fundamentally benign condition.
One application of this is in thyroid cancer, where Epstein and his team showed in a study, in the journal Thyroid, that measuring MDSCs using a flow cytometry assay could provide an improved method for doctors to estimate the risk for malignancy and the extent of cancer in patients who present with thyroid nodules.
Another promising area, Epstein said, is prostate cancer, where there is significant room for improvement in distinguishing cancers from benign prostate hyperplasia.
The technology also looks very useful for therapeutic monitoring, he added, where it could help physicians more quickly and accurately determine if a treatment is working, sparing patients unnecessary and expensive therapies, and funneling them to other options that may work better.
For these types of applications, Epstein said there is an easier argument for the cost of flow cytometry relative to the benefit to patients. For screening and early detection more broadly, he argued, the same might not be the case.
ITUS' Kumar disagreed, saying that once labs have a flow cytometry set up in place, the marginal cost to run one of its planned kits would be only in the $30 range.
"We think we can offer tests for about $100," he said, compared to the costs of circulating DNA analysis being explored by other firms, which ranges into the multiple-thousands of dollars.
Epstein maintained that the question of cost may still be an issue for MDSC-based diagnostics in broad population screening. The viability of ITUS' plans also depend on the company's ability to sufficiently validate and demonstrate its approach.
"You need hundreds of patients, or thousands if you are talking about screening, to make sure that the false-positive rate [or specificity] is clear," Epstein said. Without that, "claims for early detection seem premature," he added.
Kumar said that ITUS intends to try to partner with another company to move forward with the studies necessary to support a bid to the FDA for an MDSC-based kit, though he did not name any potential partners.
One way this could take place, he said, would be for ITUS to hook up with a ctDNA firm, with the goal of pairing their technologies. ITUS' MDSC platform would serve as a filter, identifying "hot" individuals, whose immune cell results suggest the presence of a tumor. This would then select a smaller subgroup of people to test using more expensive DNA-based liquid biopsies.
Kumar said that it's possible that other technologies could also be complementary to its MDSC approach. In both the circulating DNA space, and among immune-based approaches, there are clearly a variety of different methods being advanced — some with slight, nuanced differences from one another, and others that might overlap each other — measuring some of the same signals in different ways.
"This happens all the time in biotech. Every company for various commercial reasons goes down a particular path, but all of these measurements are related," Kumar said. "What you want is to measure what you need to measure to get the performance necessary, but to do it in a way that’s as simple as possible for the patient and as efficient and cost-effective as possible for the company."