NEW YORK (GenomeWeb) – Researchers from Caprion and Merck have identified a molecular signature predictive of the response of older adults to the hepatitis B vaccine.
Presented in a paper published last month in Nature Communications, the study identified a transcriptomic signature backed by flow cytometry and cytokine and chemokine profiles that identified patients likely to generate a weak immune response to vaccination.
As the authors noted, the signature was only moderately accurate (area under the curve of .65), but, said Caprion CEO Martin LeBlanc, the findings suggest the potential of similar approaches for use in guiding not only vaccine treatment but other kinds of immunotherapy such as checkpoint inhibitors in cancer.
He added that the research also suggests that the company's flow cytometry-based ImmuneCarta platform, which was used in the study, could prove useful in clinical projects Caprion plans to undertake in the CLIA laboratory it aims to open later this year. To date, ImmuneCarta has been solely a research tool, but, LeBlanc said, "these types of results fuel our enthusiasm for pursuing diagnostics and companion diagnostic projects" with the platform.
In the study, the researchers used a combination of transcriptomics, cell profiling, and cytokine measurements to look for differences in the immune systems of older patients who responded well to vaccination versus those who did not. On the transcriptomic side, they identified a 15-gene signature capable of distinguishing between the two sets of patients. A model combining four cell-frequency markers as measured by flow cytometry was also predictive of immune response, and increased levels of three cytokines were associated with poor vaccine response.
Broadly, the study found that higher levels of inflammatory response transcripts and pro-inflammatory cells led to a weaker response to vaccination, fitting with previous research that has suggested that constant low-level inflammation associated with aging is a cause of age-related immune senescence.
"Hyporesponse in the elderly to vaccines and other types of immunotherapies is a well-documented phenomenon," LeBlanc said, noting that a better understanding of it could be important in the development of cancer immunotherapies given that cancer is concentrated in older populations.
For instance, he suggested, a better ability to predict poor immune response due to senescence could help drugmakers distinguish between patients who fail to respond to immunotherapies due to an aging immune system versus other reasons, such as that they lack the target the therapy is attacking.
"A subpopulation that otherwise would have a 25 to 30 percent response rate might have a 40 percent or 50 percent or 60 percent response rate if you can act on the phenomena of immune senescence by figuring ways around it by priming the immune system to make it responsive to these therapies," he said. "So, I believe this sets the stage for predictive biomarkers that can help on the research side but also on the stratification side later."
With that in mind, LeBlanc said Caprion has become interested in positioning its ImmuneCarta platform for more clinical work. Currently, the Montreal-based company has primarily used its ProteoCarta mass spec-based proteomics platform for its diagnostics and companion diagnostics efforts, "but we believe that down the road our CLIA lab may well include flow cytometry," he said.
The company is also keeping an eye on the development of Fluidigm's CyTOF mass cytometry platform, an alternative to flow cytometry offering higher multiplexing but somewhat lower throughput, LeBlanc said, noting that as a company with expertise in flow cytometry and mass spec, Caprion is particularly well suited to deploying a technology like the CyTOF, which combines the two approaches.
However, he said, the company sees CyTOF as still a research tool. "What we are more interested in is when it gets more of a clinical angle to it."
With regard to its own move into the clinical space, Caprion plans to open its CLIA lab in the second or third quarter of this year, around which time it also hopes to have regulatory approval and reimbursement for a Canadian version of Integrated Diagnostics' Xpresys Lung cancer test.
Caprion in-licensed the test last year, giving it exclusive rights to market and commercialize it in Canada. Under the agreement, Caprion will pay Indi royalties on revenues generated by the test and several milestone payments tied to events like positive reimbursement decisions. The company played a significant role in the development of Xpresys, collaborating with Indi on a portion of the mass spec biomarker discovery and validation work underlying the test.
The license agreement is part of Caprion's larger strategy to use its mass spec expertise to position itself as a Canadian partner for firms looking to offer clinical diagnostics in the country.
The company is also working internally on development of its own proteomic tests, including tests for diabetes and tuberculosis that it plans to launch out of the CLIA facility.
Caprion is also working to move some of its internal pharma collaborations and companion diagnostic work into the CLIA setting as part of Phase II and III clinical trials, LeBlanc said. A major initiative driving this effort is the Personalized Medicine Partnership for Cancer project the company is heading.
Launched in 2013, the four-year project is funded by C$10 million (US$7.3 million) from the Quebec government and C$11 million from private sector participants including Caprion, Pfizer, Sanofi, Oncozyme Pharma, and TELUS Health. The initiative is using proteomic and genomic approaches to develop, deploy, and test biomarkers and therapies for lung, colon, and breast cancer.
Caprion has used funding from the project in setting up its CLIA lab and is working with the initiative's pharma partners on pharmacoeconomic studies tracking patient outcomes and performing economic evaluations of the drugs and companion biomarkers.