NEW YORK (GenomeWeb) – Liquid biopsy startup OncoCell aims to enter the cancer prognostic space with its noninvasive immuno-genomics RNA transcriptomics prognostic platform that it believes can help differentiate patients with aggressive forms of prostate cancer from patients with indolent disease.
In a feasibility study described in a poster at the American Association for Cancer Research conference in Atlanta last week, a group of researchers led by OncoCell assessed the ability of the blood-based immunogenomics RNA expression assay, dubbed Subtraction-Normalized Expression of Phagocytes (SNEP), to provide a prognostic summary for prostate cancer.
"We wanted to try and give a clinician a good picture of what you'd expect if you were to do a liquid biopsy," said OncoCell Chief Medical Officer Kirk Wojno. "We're now trying to develop a clinical test for prostate cancer that can act as a noninvasive prognosis."
The firm's SNEP platform uses an algorithm to examine changes in gene expression of two immune cell types linked to prostate cancer, phagocytic CD14 and non-phagocytic CD2 cells. The platform filters out intrinsic genomic variations unrelated to prostate cancer, and then identifies and validates prostate cancer-specific signatures.
Cofounded in 2013 in Boston by CEO Harry Stylli and Scientific Founder Amin Kassis, OncoCell began as a spinout of Harvard Medical School commercializing immunogenomics-based technology developed by Kassis' lab. Kassis' research involved extracting and comparing phagocyte and non-phagocytic cells after he noticed major differences between T-cell and macrophage landscapes in prostate cancer. He wanted to see if those differences were, in effect, specific biosignatures of disease status in a patient.
Selecting prostate cancer as its first clinical application, OncoCell later moved to Royal Oak, Michigan in late 2013 to further develop the phagocyte-based platform and collaborate with its growing urology clinical partners. Â
According to OncoCell VP of Corporate Development Geoffrey Erickson, the SNEP assay compares phagocytes and lymphocytes in a patient's bloodstream and quantifies and characterizes genomic sequences linked to aggressive prostate cancer in phagocytes. As part of the assay's workflow, researchers perform a subtractive technique by comparing patients to negative control samples, classifying patients with different levels of risk for prostate cancer based on their scores.
"By comparing genomic signature from CD14 and CD2, we can get a well-defined signature up to a couple hundred of genes," Erickson said. "Since it's a little impractical from a clinical management standpoint [to use that many genes], we do have signatures between 15 and 50 genes, which correlate to the stage of disease to each patient."
In the AACR study, the researchers initially collected peripheral blood samples — three tubes of 8 milliliters each from 713 male patients in a discovery set. They classified the patients under three major requirements: patients who had risk profiles for which tissue biopsies were recommended; patients who had biopsies greater than 90 days but less than a year before study entry and who were scheduled for but did not undergo therapy after the biopsy blood draw; and patients who were actively surveilled and would be biopsied within the next year.
The team split the blood into one-third and two-third aliquots for CD2 and CD14 cell types, and added specific antibodies in order to isolate the cells. The researchers later extracted mRNA and sequenced them from each cell type using Illumina's HiSeq platform, characterizing over 22,000 genes. They then used a final set of 10,643 transcripts with quantifiable changes to train the SNEP-based algorithm to stratify patients into groups related to their level of prostate cancer risk.
"We took genomic expression from the two cell types to estimate these scores and end points, [because] predicting only one doesn't give a full picture," Wojno explained.
To rank transcripts linked to the summaries of the biopsy — including Gleason score, cores positive, maximum involvement, and an aggressiveness index — the group tested for associations between the final set of transcripts and each of the summaries. It eventually identified genomic signatures in the discovery cohort that they later validated in two separate naïve cohorts at two time points: 305 blood samples at four hours and 470 blood samples at 72 hours post blood draw.
"We aggregated the variables together in a specific way that we did empirically that makes sense to urologists," Wojno said. "Basically, by using small volume, low-grade tumors, we could [develop] a better picture that we could provide the clinic with blood tests."
The study authors noted that the assay had a clinical sensitivity of 90 percent and area under the curve of .83. They declined to provide information on the clinical specificity.
While developing the SNEP technology, Wojno acknowledged that his team ran into issues with developing a bioinformatics pipeline for the assay. Partnering with researchers from Duke University, the firm needed to figure out how to develop an algorithm that "mathematically helped us group genes together so that they were predictive of prostate cancer risk," he said.
The authors believe that the multiple genomic signatures identified from the CD2/CD14 RNA expression ratios per assay indicated a prognostic summary that was comparable to prostate biopsy information. Prior to having a prostate biopsy, they said, the SNEP blood test could stratify patients with aggressive prostate cancer that need immediate treatment and those who are biopsy-negative and should continue to be monitored.
In addition, the study authors believe that researchers could use the assay in other liquid samples — such as urine and saliva — to track various analytes like proteins and DNA for disease prognosis.
Wojno noted that while the study used three tubes of blood, a commercialized version of the assay would only require a single tube with 8 milliliters of blood.
According to Erickson, OncoCell currently has a broad portfolio of patents and has licensed the technology from Harvard to commercialize and develop it into diagnostic tests. He declined to comment on the total amount of funding OncoCell has raised since 2013, but he noted that the firm has a "good set" of institutional and early-stage venture capital investors.
Wojno said that the firm will initially launch the technology as a lab-developed test for research use only performed at its CLIA-certified, CAP-accredited lab in Royal Oak, potentially followed by separate facilities across the US to "optimize turnaround time for physicians." The firm has performed discovery studies and is now in the process of validation and verification studies.
OncoCell believes the SNEP platform could be used in a doctor's office to detect a variety of diseases, with the prostate cancer assay eventually used by urologists or other providers who order biopsies. Erickson said the company expects to commercialize the first test within the next two years.
Competition
If and when it does, OncoCell will face competition. Several commercial and academic entities are also developing or already offer assays to help clinicians assess prostate cancer risk using liquid biopsy samples. For example, MDx Health has offered its SelectDMx assay, a urine test for prostate cancer risk stratification, since 2016. Exosome Diagnostics also offers its ExoDx Prostate IntelliScore test, which targets three exosomal RNA biomarkers expressed in men with high-grade prostate cancer.
In addition, an international group of researchers published a study in the Journal of Clinical Oncology's Precision Oncology edition in January regarding a liquid-based biopsy tool to help clinicians check patients' risk of prostate cancer.
Kassis said that SNEP stands out from other liquid-based prognostic assays because it attempts to personalize the test. When researchers compare tests using other platforms, they sample blood from a sick individual and compare it to a control. However, since individuals have unique genomic and transcriptomic profiles that are specific to their expression backgrounds, Kassis argued current technology struggles to identify disease-specific signatures.
In contrast, Kassis said that SNEP — which compares immunogenomic profiles of phagocytes and non-phagocytes — can filter out genomic background noise. This helps the assay to identify markers linked to the disease, rather than inter-individual or intra-individual differences. Â
In addition, Wojno noted that current commercial tests are limited because they only examine a gene profile from a single needle core of a much larger tumor. With the SNEP assay, he said, the phagocytic cell samples the whole tumor cell and provides a bigger picture of the condition in the patient's system.
While OncoCell hasn't determined an exact price for the SNEP assay, Wojno believes that the platform can be competitive with other genomic tests on the market. Â
Kassis noted that OncoCell also aims to explore other cancers and non-oncology conditions in the future, including Alzheimer's disease, arthritis, and type 2 diabetes, "after we get the ball rolling for prostate cancer."