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Proteona Using Single-Cell Analysis Platform to Tackle CAR T Market


NEW YORK (GenomeWeb) – With the launch this week of its first commercial assay, Singapore-based start-up Proteona aims to make inroads into the market for CAR T cell characterization.

The company offers single-cell proteomic and RNA expression analysis using technology licensed from the National University of Singapore. Called ESCAPE (enhanced single-cell analysis with protein expression), the method combines single-cell sequencing with DNA-barcoded antibodies targeting proteins of interest to allow researchers to simultaneously assess protein and gene expression.

Proteona plans to focus initially on using its assay to guide and optimize CAR T therapy but expects it will prove useful for a variety of applications including the analysis of solid tumors, said Proteona CEO Andreas Schmidt.

Proteona is currently involved in several collaborations with cancer centers around the world, including a study at Germany's National Center for Tumor Diseases Heidelberg using the ESCAPE assay to longitudinally characterize CAR T cells at the single-cell level in patients undergoing treatment.

"We are able to identify CAR T cells using [antibodies] against the CAR T cells as well as the RNA sequences, and over time we can build profiles of what happens with the CAR T cells," he said. "How are cytokines triggered? What would be a cytokine storm? What is going on in these single patients?"

The company is also using its technology to explore how different approaches to manufacturing CAR T cells make therapy more or less effective.

"Can you use a different manufacturing cycle and come up with a different batch of cells that has a different effect on the patient?" Schmidt said. "I think there will be a lot of improvement in how CAR T cells are manufactured and how consistently they are manufactured in the future."

"We have a wealth of data but [determining] what conclusions to draw out of it is, of course, a much longer process," he said, noting that the company would like to establish its technology as a QA tool for CAR T as well as possibly develop companion diagnostics based on the platform.

"Of course, something like that would take much more time, but that is the kind of thing we are looking at and the kind of partner we are eager to work with," Schmidt said.

According to Proteona, the ESCAPE platform is able to multiplex dozens of proteins at the single-cell level and combine that with single-cell RNA-seq data, allowing researchers to identify CAR positive cells and study links between their molecular profiles and their behavior and patient response to treatment.

Proteona Cofounder Jonathan Scolnick, assistant professor of physiology at Singapore's Yong Loo Lin School of Medicine and one of the inventors of the ESCAPE technology, said that currently the system multiplexes around 70 proteins per analysis but that it could in theory go much higher.

Scolnick said that the company uses the protein data primarily for phenotyping the cells that it looks at.

"There are probably 50 different types of T cells that are all distinguished based on cell surface markers, and so on the protein side we are really focused on identifying exactly what these T cell types are," he said. "And then we use the underlying gene expression to look at changes in things like cytokines."

Scolnick acknowledged that RNA levels are not always well correlated with protein expression, but said that measuring RNA allows Proteona to observe very rapid CAR T cell responses.

"When a CAR T cell, for example, sees its target, it reacts to that very quickly, and it's those changes in gene expression that are happening at that very fast timescale," he said.

Proteona is still in the early stages of demonstrating that its CAR T cell profiles can be linked to patient response, but one of its competitors in this space has found evidence suggesting that single-cell analysis could prove useful for guiding CAR T therapy.

Last year, single-cell proteomics firm Isoplexis along with researchers from Kite Pharma and the National Institutes of Health, published a study in Blood that found that the number of different cytokines expressed by T cells introduced to patients undergoing chimeric antigen receptor (CAR) T cell therapy for non-Hodgkin lymphoma correlated with treatment response.

In research presented in April, Isoplexis and collaborators at MD Anderson Cancer Center demonstrated that T-cell cytokine production was linked to immunotherapy response in leukemia patients.

Scolnick said that in addition to Proteona's CAR T work the company was using its tool to profile solid tumors and tumor microenvironments.

"One of the things we are looking at specifically in solid tumors is being able to take a holistic view of the tumor," he said. "In our assay we collect tumor cells along with stromal cells and other support cells as well as all the infiltrating lymphocytes. And that is allowing us to start to really put together a picture of what is taking place within a tumor [overall], instead of focusing only on the tumor cells or only on the immune cells or only on the stromal cells."

Other single-cell analysis companies like Fluidigm and Nanostring have developed assays that retain sample spatial information, which provides researchers and clinicians another dimension of data in their studies of things like tumor microenvironments and immune responses. Schmidt said that this was not a current focus for Proteona but that it was something it was open to exploring in the future.

Founded around a year ago, Proteona is funded by venture capital, and Schmidt added that the company planned to announce a funding round in the near future.