Arcedi Biotech aims to advance prenatal testing to whole genome, noninvasively

BioMed WorldTech

By Katie Pfaff|July 11, 2017

Arcedi Biotech ApS provides noninvasive cell-based prenatal testing options beyond traditional methods, like amniocentesis. The Vejle, Denmark-based company’s technology isolates maternal and fetal cells for more comprehensive testing and rare cell detection in fetal samples.

“This is going to be the first cell-based noninvasive prenatal test that is going to be offered,” said Ripudaman Singh, Arcedi Biotech’s CTO, to BioWorld MedTech. In a recent article published

in Biomarkers in Medicine, the firm explained its isolation of circulating fetal cells in maternal blood for detection and analysis. Their cell-based noninvasive prenatal diagnosis (cbNIPD) testing uses cells already present in the mother’s blood and may offer an alternative method for finding genetic abnormalities compared to Chorionic Villi Sampling (CVS) and amniocentesis.

The test uses a blood sample from a pregnant woman around the end of the first trimester. “Then we have developed a method where we process the blood sample. We slice all the RBCs [and] what we are left with are the white blood cells of the pregnant woman, then there are some rare fetal cells among them,” explained Singh. The cells are enriched with a proprietary antibody on a magnetic cell sorting platform. Another set of antibodies which specifically target particular fetal cells are used to stain them, and they are identified via magnification and microarray.

Fetal cells in maternal blood

“Fetal cells do circulate in pregnant women’s blood,” according to the article, “Fetal cells in maternal blood for prenatal diagnosis: A love story rekindled.”

“Even though rare in numbers, these cells can be enriched from maternal circulation and used for knowing the genetic status of the fetus. This opens up immense opportunities for prenatal screening,” according to article’s authors.

Arcedi’s test is based on prior work that indicates fetal cells’ overexpressed genes were specific in extravillous trophoblasts (EVTs), making that a target for cbNIPD. Using the EVT as a target, fetal cells can be enriched from the mother’s blood in order to screen for chromosomal and related genome changes. A gene expression array analysis of 198 fetal cells was used to identify EVTs.

Prior to identifying EVT, researchers at Arcedi first worked to separate fetal cells with a nonenrichment tactic and by reducing maternal leucocytes with a magnetic-activate cell sorting platform. However, the methods led to overexpression of placental and endothelial genes instead of maternal cells.

Cell-free options

Current methods typically enlist cell-free noninvasive prenatal testing (cfNIPD), which uses cell-free DNA in the mother’s blood. This method will show aneuploidies, or abnormalities in the number of chromosomes, but is not effective in pinpointing cop number variations (CNVs) since fetal and maternal DNA may be mixed. Authors suggest circulating fetal cells are better sources for testing to find aneuploidies and CNVs since the method uses “pure fetal genomes,” according to the paper.

“The investigation of fetal cells in maternal blood dates back to the late 1950s when the first report on circulating fetal cells was published by Alvin Zipursky,” said Singh. “Since then, a significant amount of research has been conducted to effectively isolate and assess these rare cells for use in prenatal testing, but with little success. Arcedi’s research and technology has shown that cbNIPD is a clinically viable option to determine the genetic status of the fetus. This evolving approach has the potential to change the prenatal testing space and may ultimately result in making invasive testing obsolete.”

Traditional testing methods such as cfNIPT often require additional confirmation via chorionic villus sampling or amniocentesis, while Arcedi’s method does not require additional confirmation testing, according to the company.

Other noninvasive prenatal testing methods exist on the market, typically offered by laboratories. For example, Sequenom Laboratories, of San Diego, offers carrier screening and NIPT genetic testing. The company’s tests, Maternit Genome, Maternit 21 Plus and Visibilit provide a range of information from the baby’s gender to genome-wide chromosomes, trisomy, monosomy to more specific tests like trisomy 21, trisomy 18, trisomy 13, abnormalities in sex chromosomes, sub-chromosomal and micro deletions. Gaithersburg, Md.-based Genedx also offers prenatal genetic testing based on familial conditions or for full testing requests. Tests include chromosome analysis for suspected conditions, rapid aneuploidy fluorescence in situ hybridization, prenatal chromosomal microarray, whole genome chromosomal microarray for products of conception, and additional tests for specific diseases.

While fetal cells, particularly nucleated red blood cells, were noted in maternal blood as far back as 1959, efforts to identify useful fetal cells for diagnosis and to enrich the cells for reliable testing had not advanced sufficiently until recent years. During the intervening decades, researchers had become skeptical of success in using circulating fetal cells for diagnosis, according to the article.

Testing standards

In order to maintain the quality of testing and thereby the momentum toward using such noninvasive testing of circulating fetal cells, study authors suggest that guidelines be used by those conducting tests. These include that testing with cbNIPD be targeted to a specific cell type and one that has reactive antibodies for it, the technology used to identify the antibodies should use independent parameters and platforms, and cells should be accessible for therapies. DNA also should be enriched enough to be used in next-generation sequencing and chromosomal microarray. The company is validating its research with a study among high risk pregnancies, which compares cell-based analysis and cell free NIPT and CVS. The company also plans to conduct a preclinical trial of pregnant women in Denmark in September to validate the test.