Sean Mackay, CEO and Patrick Paczkowski, VP Software, ISOPLEXIS
Sean Mackay, CEO and Patrick Paczkowski, VP SoftwareFor decades, cancer treatment has banked on surgery, radiation therapy, and chemotherapy. But what if a patient’s own immune system could be stimulated in a way that it can attack and kill cancer cells and prevent them from relapsing? Considered as the fifth pillar of cancer treatment, immunotherapy is changing the scenario by manifolds.

The most promising immunotherapies depend upon modulating various T-cells like CD8+ and CD4+ to fight against neoplastic cells. However, the means for researchers to measure effector proteins secreted by such T-cells— which determine the cellular potency against cancer—are limited today. Multiplying cancer researchers’ ability to measure such proteins efficiently and accurately, IsoPlexis is turning the tables with its next-generation therapeutic analysis platform. The company’s novel solution is redefining the way researchers can detect the amount of secreted protein at the single-cell level to better understand variations in immunocompetence of different patients. By breaking new ground in single-cell protein analysis, IsoPlexis is addressing pharmaceutical researchers’ ability to monitor patients’ T-cell function and response to therapy.

Back in 2013, when Sean Mackay, CEO of IsoPlexis, recognized the emergence of immuno-oncology, he and his Yale and Cal Tech co-founders helped caregivers analyze how immune cells could be utilized to fight cancer. To carry out the research, Mackay and his team used microchips that could analyze many more data points than existing hardware systems. Soon, the team realized that analyzing patient data from thousands of data points was an arduous task. “The tremendous inflow of data from numerous T-cells simultaneously made it challenging to understand how a cancer patient was responding to a therapy.” To address the challenge, Mackay founded IsoPlexis, creating an end-to-end system that comprehensively and effortlessly analyzes the large amounts of data coming from each patient. “The idea was to extract the actual profiles of patients from mountains of data in a summary-like format to enable biopharmaceutical companies and clinical researchers to determine the efficacy or toxicity of a therapy and help clinical researchers formulate the right combination of cancer therapies,” expresses Mackay.

Applying Big Data in Cellular Analysis to Immunotherapy

The company’s comprehensive suite of solutions is designed to help biopharmaceutical companies to create and implement solutions for effective immunotherapy, yet the original challenge was to gather the right type of data from each immune cell. IsoPlexis’ first solution, the IsoCode Chip, allows medical researchers to detect up to 42 different secreted proteins per cell across thousands of cells simultaneously, a leap in the field over traditional flow cytometry. “The additional functional proteins that we are able to see per cell have allowed us to differentiate between patients who respond to immunotherapy treatments versus those who don’t,” explains Mackay.

ISOPLEXIS: Breaking new Ground in Immunotherapy, One Cell at A Time

The idea was to extract the actual profiles of patients from mountains of data in a summary-like format to enable biopharmaceutical companies and clinical researchers to determine the efficacy or toxicity of a therapy and help clinical researchers formulate the right combination of cancer therapie

The second challenge for enabling clinical researchers to utilize this advanced technology was the requirements for automation. IsoPlexis’ imaging and automation system, the IsoLight, which images the proteins captured by the chip, and carries out the entire workflow from sample to answer enables biopharma users to focus on interpreting the data rather than executing the experiment. “It acts as a three in one system providing imaging, fluidics, and incubation at the same time,” says the CEO.

In the end, a critical element for creating a useful solution for biopharma was analytical software tools to gather meaningful conclusions from such a large amount of data per patient. IsoPlexis’ IsoSpeak software enables users to validate analyses coming from the IsoCode Chip, and streamline the processing of high dimensional data to enable comparisons amongst immunotherapy patient types, manufacturing processes, and more. Clinical researchers and healthcare professionals can capture and analyze large quantities of highly precise response data per individual cell to determine what sort of cancer immunotherapy a given patient will best respond to.

With all three solutions, IsoPlexis is able to deliver an unparalleled sensitivity in connecting and comparing many patient data points to enable improved patient stratification. Unlike existing systems that either measure cells in bulk, losing granularity, or look at only a few secreted proteins per individual cell, IsoPlexis’ technology detects critical differences in patient response based on the depth of cellular information detected. Additionally, its software suite combines and compares many patient information sets for users to draw conclusions about the immune profiles of patients that may have best chance to respond to these emerging, immune-based cancer therapies.

Embracing Recent Advances to Elevate Data in Immuno-Oncology

Today, IsoPlexis is well poised to welcome the recent advances in immunotherapy, such as CAR T-cell therapy. This rapidly maturing form of cancer treatment is highly impactful for blood cancers. CAR T-cell therapy, however, can elicit dangerously toxic reactions triggered by proteins known as cytokines. The IsoPlexis platform, being able to single out those cells that produce large amounts of cytokines, extends a strong proposition for better managing CAR T-cell therapy induced toxicities.
An apt demonstration of the proposition’s utility is the application of IsoPlexis’ solutions by Novartis to characterize and simplify the highly complex responses produced by its CAR-T products and identify key polyfunctional subsets from a pre-infusion manufacturing perspective. The aim was to analyze genetically re-engineered CAR T-cells designed to target CD19 antigens, a promising treatment for B-cell malignancies, including some types of leukemia. Using IsoCode, IsoPlexis and Novartis researchers captured new biomarker data from these CD19- targeted T-cells across multiple donors. A key takeaway of the research was the software tools IsoPlexis provided, including Polyfunctional Activation Topology Principal Component Analysis (PAT PCA) and polyfunctional heat map visualizations, as recently published in the Journal for ImmunoTherapy of Cancer. These tools allowed researchers to intuitively compare results from different donors and visualize the key combinations of proteins being secreted on a single-cell level in response to the target. “Using our next-generation software, we captured new biomarker data and developed new tools to understand this data; these can help researchers improve their products for patients who need them the most,” says Mackay.

Biomarkers: Discovering Drugs for Best Outcomes

Mackay is a seasoned entrepreneur with rich experience in the healthcare space. Following his passion for applying life sciences and information technology to enhance care delivery, he founded IsoPlexis with his co-founders at Yale and Cal Tech to accelerate the fight against cancer. With his leadership team, he has been steering the development of multiple immuno-oncology response detection techniques to advance single-cell precision medicine solutions. Following its model to help clients “elevate their data with predictive single cell response,” the company will continue empowering researchers and biopharmaceutical companies to provide therapies that invoke positive clinical outcomes.

The company aims to continue impacting the immuno-oncology space. With a continued focus on enhancing the broader manufacturing processes for genetically re-engineered CAR T-cell therapies, IsoPlexis plans to establish biomarkers for the newly approved therapies for cancer. “We will continue to help biopharmaceutical companies with the analysis of these cell therapies and stratification of different patient cohorts according to various biomarkers. We will utilize that information to figure out the type of immune drugs that exhibits the best and least toxic outcome for a patient.”

Hinting at the evolving scope of immunotherapy, beyond cancer, to also treat diseases like infectious and neurodegenerative ones, Mackay says, “We will also be focusing on creating solutions for the upcoming areas of immunotherapy in the coming days.”