NEW YORK (GenomeWeb) – Omics firm IsoPlexis is developing an automated version of its single-cell analysis platform for use in large clinical trials of CAR-T therapies for blood cancers.
The Branford, Connecticut-based company is using a $1.8 million grant it received this summer from the National Cancer Institute's Small Business Innovation Research program to fund development of the automated system.
IsoPlexis plans to initially implement the automated platform at clinical trial sites around the country where researchers can use it to run the company's single-cell cytokine panel to help identify expression signatures linked to patient response to CAR-T treatment and other re-engineered T cell therapies, said Sean Mackay, the company's co-founder and CEO.
IsoPlexis launched in 2014 as a spin-out from the lab of Rong Fan, associate professor of biomedical engineering at Yale University. The technology underpinning the system was originally developed in the lab of California Institute of Technology researcher James Heath, where Fan was a postdoc. Heath is a director at IsoPlexis and member of its scientific advisory board.
The company's platform uses microchips featuring arrays of thousands of microchambers which isolate individual cells from samples of interest. These chambers are then sealed with a slide patterned with groups of antibodies in a number of different spatially isolated lines. This allows the researchers to identify proteins based on the color of fluorescence produced upon binding and the location on the slide where the binding event occurs. In this way, they can multiplex far beyond the levels allowed by fluorescence readout alone, which has traditionally topped out at around four analytes (though recent advances in single-cell technology like mass cytometry have enabled multiplexing of dozens of proteins measurements in single cells).
In a study published in Proceedings of the National Academy of Science in 2014, a team led by Fan demonstrated the use of the platform to measure 42 immune effector proteins in single cells.
Mackay said the company currently offers a 32-plex single-cell cytokine panel that is the focus of its engineered T cell work and will be the first panel offered on the automated platform it is developing.
"We're trying to meet the customer demands that we see in the field because the complexity of these T-cell therapies and the need for better characterization [of therapeutic T cells] has become apparent," he said.
Heath and collaborators demonstrated the potential of the technology for such work in a 2013 paper in Cancer Discovery in which they profiled the cytokine expression of re-engineered T cells, identifying what they called "polyfunctional" T cells that they hypothesized could be the main drivers of antitumor immune response.
These cells – which the researchers defined as producing five or more cytokines upon stimulation – represented on average only 10 percent of a given cell type but secreted roughly 100 times the amount of protein than the other 90 percent of the cell population. They also observed that differences in these cells between patients appeared to track with response to therapy.
Mackay noted IsoPlexis has been using the panel in work with pharma customers including Novartis and Kite Pharma (owned by Gilead) to help assess how patients will respond to re-engineered T cell therapies developed by these companies.
At the 2017 American Association for Cancer Research annual meeting the company with collaborators from Kite Pharma presented data from a study using the platform and cytokine panel that found that cytokine expression of anti-CD19 CAR T cells were linked to response to this therapy in patients with advanced non-Hodgkin's lymphoma.
In a poster presented at this year's Federation of Clinical Immunology Societies annual meeting, researchers from IsoPlexis and Novartis presented data from work that identified a diverse range of cytokine responses from CD 19 CAR-T cells when challenged with anti-CAR antigens.
The studies, MacKay noted, indicate the company's platform has potential to identify cytokine expression patterns that could predict the effectiveness of CAR-T and other T cell therapies.
Now, he said, the goal is to integrate the chip-based system "into an automated imaging platform where clinical researchers can run the entire workflow."
"There's a target market that we work with on a regular basis in the clinical research area, and their work would be enhanced by an automated system because they can then test more patient samples in higher throughput," he said. "They can instead focus on the data output knowing not only that there's a level of reproducibility within the system [due to eliminating manual steps], but also that they don't have to spend the time to learn the technique."
While using the cytokine panel for research into re-engineered T cell therapies is currently IsoPlexis's primary focus, the company is also planning collaborations around phosphoproteomics analyses enabled by the platform, Mackay said.
He cited another study led by Heath, this one published last year in Cancer Cell, in which the researchers used the platform to detect changes in protein phosphorylation patterns in glioblastoma cells as early as 2.5 days after drug treatment.
Identifying alternate pathways activated due to drug treatment allowed the researchers to add another therapy targeted toward that second pathway, which proved effective in shutting down tumor growth in mouse models.
IsoPlexis is also working to expand its test menu into immune-oncology, autoimmune disease, and infectious disease, Mackay said.
The company, which currently has 34 employees, will fund these efforts with $13.5 million in Series B financing it closed last month in a round that was led by Spring Mountain Capital and included Connecticut Innovations, North Sound Ventures, and Ironwood Capital.
Mackay said the funds would also go toward building out the company's operations team to handle the increased demand for consumables and other components it expects to see as it begins placing automated versions of its platform.
The company is also working on "some next-generation products that hopefully we'll be talking about next year," he said.