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Vitra Seeks Partners to Bring Primary Cells, RNAi Apps to CellCard Tech

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Having gained a foothold in drug discovery for its CellCard multiplexed cell-based assay system, Vitra Bioscience is now looking to extend its flagship technology to primary cell applications, CBA News has learned.

Vitra has initiated what it calls the Primary Cell Program, in which it hopes to seek pharmaceutical partners as collaborators to investigate the use of CellCard to assay primary cells from multiple patients in an effort to assess population variation in vitro in the pre-investigational drug-discovery stage, company officials told CBA News last week.

"We're seeking collaborations with large pharma to do these studies based on the ability of the platform to miniaturize assays of primary cells," said Simon Goldbard, Vitra's founder and vice president of product development. "We're seeking larger studies and more high-value studies than just selling our systems, and the reason is because this area is becoming really important and starting to get a lot of attention, and we consider this to be a very high-value proposition."

Goldbard said the company has seen an increased level of interest from current and potential pharmaceutical customers to extend CellCard to primary cells. This was capped, he said, by the near-standing-room-only question and answer session that Goldbard chaired on using primary cells versus immortalized cells in drug discovery two weeks ago at the World Pharmaceutical Congress in Philadephia.

In fact, Goldbard presented data in a separate session at the conference from a study Vitra conducted in collaboration with primary cell provider Cambrex Bioscience, in which scientists from the two companies looked at the effect of a variety of glitazones on human primary adipocytes from 10 different patients. Glitazones comprise a family of drugs used to manage diabetes.

The data demonstrated that there was distinct variability in how the adipocytes responded, proving that the CellCard system could be used to assess patient variability prior to clinical trials.

"That's some really huge data, and that's the kind of stuff that convinced large pharma to initiate talks with us," Goldbard said. "This is new territory for everyone involved here. Everyone likes the concept of the in vitro predictability of primary cells over, for example, animal models. We just need to correlate clinical data — everything makes perfect sense, but we still need to prove that there is a connection with clinical data. That's what we want to do with pharma."

John Schneider, Vitra's head of marketing and business development, added that "we have two other current sales situations where our customers have come right out and said that they'd like to do this with primary cells as well as regular cells, because they knew we had done the experiments.

"So we see the demand, the customers are asking us for it, and we're actually working with them more collaboratively to develop the technology," he added. "So when it's transferred over to them and they start running it, we'd like to see close to 100 percent chance of success; rather than transfer something over where they don't have the skills in house."

Taosheng Chen, a senior research investigator in the lead discovery division at Bristol-Myers Squibb who has conducted studies using CellCard (see CBA News, 11/2/2004), last week told CBA News that using primary cells with CellCard would likely be useful.

"I haven't used primary cells in my own evaluation of the technology, so this is pure speculation," he said. "I think it would be useful, because primary cells are usually very hard to get and usually very expensive, and one of the advantages of the technology I have found is that you can use a very small number of cells compared with typical assays. So there could be a big savings."

Chen said that primary cells are used in many stages of drug discovery, depending on the disease model. "Toxicology and liver toxicity is definitely one of the fields. It's definitely not for high-throughput screening, but for target validation and toxicology screening, I think people are using them a lot."

Special Expertise

According to Goldbard, the specific expertise needed to conduct CellCard assays using primary cells is actually not too hard to come by. In fact, researchers would face essentially the same challenges they do using primary cells in any type of cell-based assay: different media and care, mostly.

On the CellCard, things might actually be a bit more complicated, because the idea is to have several types of cells — each cultivated on its own miniature CellCard carrier device — mixed into one well with common media in order to achieve multiplexed assays. Where one type of media may be suitable for some primary cells, it may not for others. This may limit Vitra to multiplexed assays of varying strains of one or two types of primary cells.

Goldbard said that Vitra is at first targeting a few types of primary cells with the program, including adipocytes and pre-adipocytes for the diabetes drug-discovery market; HUVEC and other related endothelial cells for cardiovascular diseases; renal cells for toxicology studies; and fibroblasts for oncology.

In a related development, Vitra has been collaborating with Sanofi-Aventis since late last year to test the feasibility of high-throughput multiplexed RNAi-based screens on the CellCard system, as well as explore the use of primary cells.

"In past [work] that used RNAi with other cells, our collaborators — Sanofi-Aventis in this case — tried to tie this in with gene-expression arrays," Goldbard said. "We were doing the phenotypic assays, and they were doing the counterpart, the gene-expression arrays. So now we're combining these two things, too, into another study, where we're talking with one large pharma to actually do that kind of study on primary cells, across different patients, and bringing in RNAi."

Goldbard declined to disclose the identity of its potential new partner.

It is also unclear whether Sanofi-Aventis and Vitra will continue to work together, however. Goldbard said that Vitra was "in the midst of formulating how we might move forward" with the Sanofi-Aventis collaboration. Calls to Sanofi-Aventis were not returned in time for publication.

However, Goldbard said that Vitra will continue its collaboration with Cambrex. "We're still working with them, and that collaboration is in pretty good shape," he said. "They supply primary cells. There are other companies that do this, but if we want to do large clinical studies, they're set up to do something like that."

Although Vitra's initial aim is to flesh out the potential value of primary cell and RNAi applications on CellCard, Schneider told CBA News that the long-term goal would be to increase sales of the CellCard system.

"At this point, it's difficult to [determine] at what point this is a mainstream product," Schneider said. "We can do it, and we've got experience looking at both primary cells and RNAi transfection as applications, but there's a pretty big gulf between folks who have done a lot of this, and folks who are just learning.

"Doing it with collaborators just ensures that they are getting the benefit of our experience as well as the platform," he added. "We do envision at some point, when the protocols have been optimized enough, that we can transfer the technology to the customers' hands so they can do it themselves. We're just not sure at what point that is right now. It's pretty new stuff for everybody."

— Ben Butkus ([email protected])

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