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Proteona Driving Adoption of Immune Profiling Platform for CAR-T, Multiple Myeloma Research

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NEW YORK – Single-cell omics firm Proteona is working to drive adoption of its immune profiling platform with data from a recently published study and grant awards to two scientists using the company's tools to study the disease.

Last month, the Singapore-based startup said that it had awarded a pair of $50,000 grants to two multiple myeloma researchers: Scott Goldsmith at and the Washington University School of Medicine and Florian Kuchenbauer at Canada's BC Cancer Research Centre.

The company and collaborators also last month published a study in Science Advances that used its platform to characterize chimeric antigen receptor (CAR)-T cells generated via a novel plasmid-based approach that its developers hope could prove a safer, easier, and more effective method of producing these cells.

Traditionally, CAR-T cells are made using lentiviruses to transfer genes in T cells, which raises the risk of toxicity and can also lead to side effects due to genomic integration of the virus that reduce the cells' therapeutic effectiveness, said Patrick Schmidt, project leader at the National Center for Tumor Diseases (NTC) in Heidelberg, Germany and an author on the Science Advances paper.

To address these challenges, Schmidt and his colleagues developed an approach to engineering T cells that uses plasmid-based vectors. In their Science Advances work they demonstrated that such vectors, which they termed nanovectors, could be used to manufacture CAR-T cells at the scale needed for clinical use and that they exhibited stronger anti-tumor activity in vitro and in mouse models than did CAR-T cells generated using conventional techniques.

The researchers used Proteona's technology to molecularly characterize the new CAR-T cells and understand how they were different at the genomic and proteomic levels from conventional CAR-T products.

Proteona's ESCAPE (enhanced single-cell analysis with protein expression) technology, licensed from the National University of Singapore, combines single-cell sequencing with DNA-barcoded antibodies targeting proteins of interest to allow researchers to simultaneously assess protein and gene expression.

The platform "was able to give us really a good feeling for how our T cells look compared to lentivirus-transduced ones, and it turns out that they look, simply, more physiologic, more healthy," Schmidt said.

He said, for instance, that in the lentivirus-transduced cells the researchers observed heightened expression of viral response genes, which, he noted, is not unexpected. Those genes did not exhibit heightened expression in the plasmid-based cells, which Schmidt said enhanced their anti-tumor effectiveness.

Prior to the rise of single-cell omics technologies like Proteona's over the last several years, CAR-T researchers commonly used tools like flow cytometry to assess cells' effectiveness, looking, for instance, for the presence of the desired chimeric antigen receptor on their surface.

"Maybe we would see that in our product the CAR is more expressed, but just having more molecules on the surface doesn't necessarily mean that your product gets better," Schmidt said. "The resolution was simply not sufficient for us."

"Having a multi-omic approach we can for the first time really underpin our speculation that when we produce cells with a non-viral system they are healthier and better," said Matthias Bozza, a postdoctoral researcher at the German Cancer Research Center (DKFZ) Heidelberg and first author on the study.

"We have been for years saying that if you use a virus it is harmful for the cells, but we have not really been able to support our speculations," he said. "Now for the first time we can really say, this is what we think, and here is the data."

Bozza noted that it remained to be shown that nanovector-based cells performed better in patients, "but for the first time we can really measure the fitness of the cells after gene delivery."

Schmidt said that the Proteona analysis clearly distinguished between the viral and nanovector cells and added that it was not a matter of a handful of genes that were differentially expressed but rather "a couple of hundred."

Schmidt said that he envisions single-cell analysis tools like Proteona moving into the clinic to enable both monitoring of CAR-T products in patients and the patient response to the therapy.

Bozza said that he and his colleagues are now working to manufacture the nanovector cells in a GMP environment and have acquired a grant to fund testing of their manufacturing protocol in five multiple myeloma patients.

"When we get results from these five patients we will go to regulators" with the goal of launching a clinical trial for the therapy, he said.

Andreas Schmidt, Proteona's CEO, said that in addition to characterizing CAR-T products, the company believed its platform would prove useful for guiding cancer treatment, citing as an example multiple myeloma where he said it was able to monitor patients pre- and post-treatment and follow the different clones of the tumor.

The company aims to further demonstrate the utility of its platform in multiple myeloma with the grants it awarded to Wash U's Goldsmith and the BC Cancer Research Centre's Kuchenbauer. The grants provide the researchers each with $50,000 in research services from Proteona.

Goldsmith's research focuses on overcoming drug resistance in multiple myeloma patients. He is working to validate potential markers of drug resistance in the disease and is using the Proteona platform to look at multiple myeloma subpopulations at the single-cell level with the aim of better understanding mechanisms involved in resistance and identifying drugs that might help overcome it.

Kuchenbauer is using Proteona's technology to refine a classifier it has developed to identify patients unlikely to respond to standard first-line treatments for multiple myeloma.

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