The power of ‘poly’ in CAR-T

Clinical data highlighting single-cell polyfunctionality as a potential predictor of patient response to CAR-T cell therapy published in journal

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BRANFORD, Conn.—According to IsoPlexis Corp., research recently published in the journal Blood—conducted in a collaborative effort with Kite Pharma, a Gilead company—demonstrates a significant association between the functionality of an anti-CD19 CAR-T cell product before treatment, as defined by IsoPlexis’ Polyfunctional Strength Index (PSI), and the objective response in patients with non-Hodgkin lymphoma (NHL).
As the summary of the Blood paper—titled “Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL”—notes of what is gleaned from the data:
  • The polyfunctionality strength index of manufactured CAR-T cells were associated with clinical response and toxicities
  • Monitoring CAR-T cell polyfunctionality as a key product attribute may complement other characteristics including T-cell proliferation
Or, as IsoPlexis puts it, “The results highlight the potential to predict whether cancer patients will respond to CAR-T cell therapy before treatment, as well as to improve both pre-infusion product potency testing and guide cell product optimization.”
Researchers used the IsoCode, IsoPlexis’ single-cell precision engineering platform, to analyze CAR-T cell therapy products from 20 patients with NHL. The IsoCode Chip provides an integrated solution for detecting functional cellular responses with single-cell resolution. The system can capture a previously unseen 42 different secreted functional proteins per cell, with known immune activities, across thousands of single cells simultaneously. Furthermore, IsoPlexis’ IsoSpeak informatics software enables researchers to generate a precise, functional patient profile from this data to better understand and predict complex patient response to cancer immunotherapies.
Using this technology, researchers captured data to determine the PSI of each product, and this metric was associated with complete or partial patient response to the anti-CD19 CAR-T cell product.
According to IsoPlexis, other pre-infusion metrics that were tested in this study were not found to be predictive.
“We were excited to collaborate on this groundbreaking research,” said IsoPlexis CEO Sean Mackay. “Using our single-cell predictive profiling platform, leading oncology and immunotherapy researchers and clinicians were able to collect this data, which demonstrates a potential to be able to apply the right therapies to the right patients and continue to personalize cancer immunotherapies, as these therapies continue to provide significant benefits to patients worldwide.”
Dr. Adrian Bot, Kite’s vice president for translational sciences, added: “Through this research, we were able to highlight the important role a functionally versatile subpopulation of CAR-T cells may play in the fight against cancer. This could lead to new methods to optimize T cell products.”
For those who want to delve a bit more into the technical details, the abstract of the paper notes, “After treatment with chimeric antigen receptor (CAR) T cells, interleukin (IL)-15 elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines including interferon-γ (IFN-γ), IL-17A, IL-8, and macrophage inflammatory protein 1-α.
“A prespecified T-cell polyfunctionality strength index (PSI) applied to preinfusion CAR product was significantly associated with clinical response, and PSI combined with CAR T cell-expansion or pretreatment serum IL-15 levels conferred additional significance. Within the total product cell population, associations with clinical outcomes were greater with polyfunctional CD4+ T cells compared with CD8+ cells. Grade 3+ cytokine release syndrome was associated with polyfunctional T cells, and both grade 3+ neurologic toxicity (NT) and antitumor efficacy were associated with polyfunctional IL-17A–producing T cells. The findings in this exploratory study show that a preinfusion CAR product T-cell subset with a definable polyfunctional profile has a major association with clinical outcomes of CAR T-cell therapy.”

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