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Institut Pasteur Building Baselines of Immune Response Using Myriad RBM's TruCulture System

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Researchers at France's Institut Pasteur are using Myriad RBM's TruCulture blood collection and culturing system to characterize the immune responses of 1,000 healthy individuals.

The effort aims to establish a baseline of healthy immune response that could be used for purposes including diagnostic and drug development.

Last week, the researchers published in the journal Immunity an initial analysis of data from 25 study participants. Among the most notable of their findings was the identification of an immunological phenotype in two subjects characterized by a failure to release the cytokine interleukin-1α.

According to Ralph McDade, president of Myriad RBM, this finding has held in the larger 1,000 patient dataset, as well, presenting in around 8 percent of the study population.

Beyond the specific findings of the study, the work demonstrates Myriad RBM's TruCulture technology, which, McDade told ProteoMonitor, offers the ability to measure an individual's immune response with a reproducibility typically not achievable by conventional methods.

This reproducibility, he said, allows researchers "to really characterize what a normal person's immune response looks like and how much variability there is between people. In the past we haven't been able to do those experiments because there was so much variability in [traditional] techniques."

The TruCulture system uses individual, self-contained tubes for whole blood collection and culture. The tubes are functionalized with various immune stimulants, allowing researchers to investigate response to these stimulants. Once taken and cultured in the TruCulture tubes, the blood sample can be spun down, separating out the cells for analyses including gene expression and flow cytometry experiments and the supernatant, which can then be analyzed for protein expression.

The method was developed in 2006 by German-biotech firm Experimental & Diagnostic Immunology, which RBM acquired in 2007. The company has marketed the technology since 2008 as an alternative to techniques like peripheral blood mononuclear cell culturing, McDade said.

PBMC analysis has been the standard approach for measuring immune response in areas like drug development. The method, however, suffers from complexity and a lack of reproducibility, McDade said.

"For many years, if a pharmaceutical company had a question about what their drug was doing to immune response" they used the PBMC approach, he said. "This required that you take the sample from the person receiving the drug; you chill it down; you ship it to a central lab; the lab pulls this sample out that is now 12-plus hours removed from the body, and they go through a 14- to 17-step process to isolate the PBMCs. Then they put those in a culture and they stimulate them and they ask the question, before and after the drug, 'are those cells more or less stimulatable.'"

The complexity of this process. McDade said, leads to "extreme variability."

With the TruCulture system, the collection and culture tubes are first prepared by Myriad RBM, functionalized with the stimulants under investigation, and then sent to the research site, where the analysis can be done without having to transfer the samples to a central lab or remove the PBMCs for culturing.

This, he noted, leads to improved reproducibility, which, in turn, allows for the sort of healthy immune profiling being performed by the Institut Pasteur group.

"The literature is full of data from PBMC [analyses], and there is lots of data on PBMC work with normal individuals," McDade said. "But there has been very little in TruCulture. And what we think this is going to do is make people realize that this is so reproducible that we can now ask very specific questions."

The Immunity study looked at response to 27 different immune stimulants including medically relevant bacteria, fungi, and viruses; agonists specific for defined host sensors; clinically employed cytokines; and activators of T cell immunity. The effort aims primarily to establish a baseline for "normal" immune response for future research use, but, in doing so, could suggest some specific lines of inquiry worth pursuing.

In the case of the IL1α finding, for instance, past research has suggested that some people don't release the cytokine, but, McDade said, "no one would have expected that high a percentage."

"There is IL1α and IL1β, and they do redundant tasks, so perhaps a person who doesn't make the alpha is fine if they make elevated beta," he said. "But they are different genes. So, is there something about that phenotype that makes people more or less likely to have infectious disease, or more or less likely to have a cancer? Those are the kinds of questions that TruCulture will allow people to ask."

While the company has marketed TruCulture since 2008 and used it in collaboration with a number of pharmaceutical firms, McDade said he believed the growing interest in immunomodulation therapies for diseases like cancer and autoimmune disorders could lead to an increase in demand for the product.

One primary use for the system could be as an ex vivo tool for determining immune response to immunomodulators before testing them in human subjects. It could also prove useful for comparing drug responders to non-responders in companion diagnostic development work.

Another area Myriad RBM sees as a target for the technology is vaccine work, McDade said.

"One of the problems in vaccinations is how do you know the vaccine worked," he said. "In situations where you are strictly looking for an antibody response, you can just take the blood and look for antibodies, but the problem going forward is soon the antibody response is no longer detectable. But the immune response is still present, so we can go back months or years after your vaccination and stimulate with that vaccine and see the response in the tube."

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