CAR-T Clinical Response Biomarker Discovery

Precision Profiling™ has shown that highly functional subsets of cytokine response may provide strong predictive biomarkers of clinical response. IsoPlexis is able to characterize the functionality of anti-CD19 CAR T cells in detail and at a single-cell level, by analyzing their co-production of 30+ cytokines. This allows for accurate measuring and characterization of the product T cell polyfunctionality, spanning a panel  key immunologically relevant molecules across homeostatic/proliferative, inflammatory, chemotactic, regulatory and immune effector categories. In past research, IsoPlexis has used this functional characterization of CAR-T cells to discover promising potential correlates to clinical outcome of patients undergoing CAR-T therapies.

IsoCode Data

Figure 1: Patient single-cell CAR-T product PSI associated significantly with clinical outcome (Rossi 2017).

Figure 2: CD4+ CAR-T example showing non-redundant cytokines contributing to PSI differences (Rossi 2017).

Publications

Rossi J, Paczkowski P, Shen Y, Morse K, Flynn B, Kaiser A, Ng C, Gallatin K, Cain T, Fan R, Mackay S, Heath JR, Rosenberg SA, Kochenderfer JN, Zhou J, and Bot A. Polyfunctional Anti-CD19 CAR T Cells Determined by Single-Cell Multiplex Proteomics Associated with Clinical Activity in Patients with Advanced Non-Hodgkin’s Lymphoma. Presented at AACR 2017, Session MS.CL10.01 - Clinical Biomarkers.

Lu Y, Xue Q, Eisele MR, Sulistijo E, Brower K, Han L, Amir ED, Pe’er D, Miller-Jensen K, and Fan R. Highly Multiplexed Profiling of Immune Effector Functions Reveals Deep Functional Heterogeneity in Response to Pathogenic Ligands. Proc. Natl. Acad. Sci., 112 (7), 607-615 (2015).

Lu Y, Chen JJ, Mu L, Xue Q, Wu Y, Wu PH, Li J, Vortmeyer AO, Miller-Jensen K, Wirtz D, and Fan R. High-throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity. Analytical Chemistry, 85 (4), 2548– 2556 (2013).

Ma C, Fan R, Ahmad H, Shi Q, Comin-Anduix B, Chodon T, Koya RC, Liu CC, Kwong GA, Radu CG, Ribas A, and Heath JR. A Clinical Microchip for Evaluation of Single Immune Cells Reveals High Functional Heterogeneity in Phenotypically Similar T Cells. Nature Medicine, 17, 738-743 (2011).

CAR T Cell Functionality Found to Correlate With Outcomes for Patients With NHL. "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, leading to new ways to characterize and optimize T-cell products," Adrian Bot, MD, Kite’s vice president, Translational Medicine, said in a statement. "These insights were made possible by using the IsoPlexis technology."

IsoPlexis Research, in Collaboration with Oncology Specialist Kite Pharma, Offers Hope for Targeted CAR-T Treatment. US-based biotech firm IsoPlexis has presented findings from research using the company’s precision engineering platform, called IsoCode. The data show the potential to predict whether cancer patients will respond to CAR-T cell therapy prior to treatment, as well as to improve both pre-infusion potency testing and cell product design.

CAR T Cell Functionality Correlates With Outcomes, Offering a Biomarker for Response. The flexibility of CAR T cells to perform multiple functions was associated with the level of clinical activity elicited for patients with advanced non-Hodgkin’s lymphoma (NHL). For the biomarker assessment, PSI was determined by an analysis of pre-infusion CAR T cells using a single-cell, high-multiplexing ELISA system developed by IsoPlexis.

IsoPlexis and Kite Pharma Report Clinical Biomarker Data at AACR. IsoPlexis collaboration offers breakthrough insights into detecting and predicting patient response to t-cell therapy. Data captured by IsoCode, IsoPlexis' single-cell precision engineering platform, detected a statistically significant association between the potency of CAR-T cell product prior to treatment and objective response of cancer patients post-treatment. The results highlight the potential to predict whether cancer patients will respond to CAR-T cell therapy prior to treatment, as well as to improve both pre-infusion potency testing and cell product design.

IsoPlexis Awarded NIH SBIR Grant to Develop Single-Cell Analysis Platform to Facilitate Cancer Immunotherapy. IsoPlexis was recently awarded a competitive Phase I Small Business Innovation Research (SBIR) grant from the National Cancer Institute of the National Institutes of Health to develop a multi-protein, single-cell analysis platform to facilitate personalized cancer immunotherapy response detection.

Contact us to find out more about how IsoPlexis can help your organization.