Single-cell multi-omics confirms high levels of CAR expression and low immunogenic profile of a novel CAR-T product

Proteona, a Singapore-based single-cell precision medicine company, has announced the publication of the results of a long-term collaboration with researchers at the German Cancer Research Center (DKFZ) and its National Center for Tumor Diseases (NCT) to develop and characterize an innovative non-integrating CAR T vector system. The study, published in the journal Science Advances, characterized the novel CAR T cells using Proteona’s ESCAPE™ CAR T assay, a single-cell multi-omics product designed for in-depth characterization of CAR T cell therapy products and patient samples.

While CAR T cells are traditionally made using viral vectors, the DKFZ researchers were able to develop a novel method to make CAR T cells using engineered DNA vectors that cut the production time by two weeks and reduce viral vector-related toxicity. To compare CAR T cells made using the new method to those made with conventional methods, the researchers used Proteona’s ESCAPE CAR T assay to comprehensively compare cell populations across thousands of measurements per cell. They found that the novel CAR T cells are more similar to unmodified T cells than they are to traditionally produced CAR T cells and, that genes showing the largest expression differences between the novel and traditional CAR T products relate to low immunogenicity and high cancer-killing capacity. Flow cytometry, the most commonly used analysis in CAR T production, could not differentiate between the two types of CAR T cells.

“For a complex product like CAR T, it is extremely important to fully understand the cells beyond what is on the surface. The gene expression variations that ESCAPE picks up can translate into differences in clinical responses. Single cell multi-omics will be essential for adding precision and control into cell therapy development and manufacturing. We are very excited to pioneer this trend and to contribute to this new, safer, cell therapy for cancer patients,” said Dr. Andreas Schmidt, CEO of Proteona. “Beyond that, we are seeing tremendous demand in using our products to monitor what happens to those CAR T cells after they are given to the patients, and how the patients’ immune and tumor cells respond in real-time.”

Proteona was the first company to provide a commercial single cell multi-omics assay specifically designed for CAR T cell analysis. The assay comes with a panel of 25 antibodies that measure key protein markers required for CAR T cell characterization. Simultaneously, it measures the expression of thousands of genes, providing rich data for detecting subtle biological differences. Proteona supports data analysis with MapSuite™, a collection of artificial-intelligence-based tools and a curated single-cell disease database that accelerate data analysis and interpretation.

“As early adopters of the ESCAPE CAR T assay, we find it extremely valuable to be able to obtain an in-depth understanding of CAR T samples on a single cell level,” said Dr. Patrick Schmidt, co-author of the publication and Principle Investigator at NCT Heidelberg, DKFZ. “Using only a small amount of blood or bone marrow samples, we get not only an overview of the CAR T cell persistence but also a snapshot of an individual CAR T cell’s activation status and characteristics. This is the most comprehensive tool available both for quality control and for monitoring patient response in clinical studies.”

“This publication not only opens up a new way of efficient, cost-effective CAR T cell manufacturing but also highlights the importance of careful characterization of cell therapy products,” commented Dr. Andreas Schmidt. “Single-cell multi-omics can help us select the most suitable CAR T product, understand the patient response, and in the future, truly tailor treatment to the individual patients.”

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