Single-Cell Biomarker Symposiums: Cutting Edge Single-Cell Proteomics Insights in Immunotherapy

Overview

True functional immune cell biology is key to understanding and combating many of the world’s most complex diseases. IsoPlexis’ data has made and continues to make an impact in cell and combination immunotherapies and biomarker strategies in oncology. These novel insights were highlighted recently at several Single-Cell Functional Biomarker Symposiums in California, Texas, and Massachusetts. Leaders in immuno-oncology demonstrated their pioneering data generated with IsoPlexis’ true functional biology. We are thrilled to share some of the amazing accomplishments that were presented during these inspiring events!

Attendees of these symposiums learned how leaders use single-cell functional proteomics to understand the heterogeneity of immune response and how these findings are being applied to determine mechanisms of response to cancer immunotherapies. Those who attended also learned more about IsoPlexis’ systems and next generation applications across immunology.

Between these three symposiums, we had over 110 pre-registered attendees! Read on to find out more about the findings shared at these events.

CAR-T Cell Therapy and Next Generation Development

The analysis of CAR-T cells prior to infusion can guide and help anticipate patient response. This data provides feedback to control the manufacturing process and optimize engineered T cell potency. Polyfunctional single-cell analyses provides powerful tools for such optimizations.

In this area, we learned about:

  • The functional assessment of CAR-T production ramifications for distributed production and multi-targeted CAR-T therapy, presented by Dr. Dave Miklos of Stanford University. Dr. Miklos also discussed the need for single cell cytokine analysis to explore T cell exhaustion in the context of adoptive cell therapies using CAR-T approaches.
  • Exciting new findings in designing next generation regulatory T cell immunotherapies for autoimmunity and organ transplant rejection were presented by Dr. Leonardo Ferreira of UCSF. Dr. Ferreira also talked about the application of single cell cytokine analysis in the characterization of T regulatory based CAR-Ts for autoimmune diseases like diabetes.

Checkpoint and Combination Therapy

Assessing metrics such as critical quality, variability, functional attributes driving efficacy, safety, and potency has proven difficult given cell product heterogeneity, yet there is an additional need to understand which cytokines are being secreted to eliminate the tumor. Some of the presentations in checkpoint and combination therapies included:

  • Seth Pollack of Fred Hutchinson Cancer Research Center’s use of IsoPlexis technology following adjuvant therapy and association of polyfunctionality with TCR diversity in pre-treatment soft tissue sarcoma (STS) patients. The use of IsoPlexis’ novel single cell cytokine analysis and its correlation with TCR diversity in immune monitoring and intratumor injection of a TLR4 agonist in STS were also among the topics discussed by Dr. Pollack. The pre-treatment CD4 PSI positively correlated with the TCR diversity of PBMCs (p = 0.0185).
  • Johanna Kaufmann of Tesaro/GSK discussed the increased polyfunctionality found in TILs following double and triple checkpoint therapies. Triple combination treatment was able to significantly increase the PSI of both subsets by 2.9 and 3.7-fold, respectively (p < 0.001).
  • Barbara Sennino from PACT spoke about finding in developing personalized neoTCR-T cell therapies comprising polyfunctional CD8 and CD4 T cells for patients with solid tumors.

Checkpoint Biomarkers

Polyfunctional biomarkers reveal the uniquely correlative T cell specific mechanism in a variety of therapeutic areas: checkpoint therapy, combination agonists, double/triple combination checkpoint, and immune fitness. PSI reveals these unique correlates in the blood as well, which presents a more actionable and accessible source of sample in cellular cancer vaccines, checkpoint therapy, combination vaccines, bispecifics, and TCR-T cell therapies.

We heard from:

  • Michael Andreef of MD Anderson Cancer Center, who presented an overview of strategies for biomarker identification in patients with AML, identified to have p53 mutations. Newly diagnosed, untreated patients with AML carrying TP53 mutations showed a pronounced decrease in PSI (p = 0.013).
  • Naval Daver, also from MD Anderson Cancer Center, has been employing IsoPlexis’ Platform towards developing biomarker strategies for optimizing checkpoint therapy. Dr. Daver provided an overview of current biomarker strategies for guiding the use of combination checkpoint immunotherapies in blood cancers. He also shared the correlations found using IsoPlexis’ system between the PPSI of newly diagnosed and relapsed AML including a strong survival correlation of patients with PSI greater than 10 treated with azacytidine/nivolumab.
  • Aaron Foster, PhD, of Bellicum Pharmaceuticals discussed assessing polyfunctionality and performance in their next generation GoCAR-T cells with the use of IsoPlexis’ technology to characterize their novel GOCAR-T products, incorporating safety switches.

Novel CAR-T Constructs and the Next Frontier

Together, the IsoLight and IsoSpeak can provide a more sensitive and comprehensive functional assessment of CAR-T pre-infusion products to evaluate the efficacy of CAR-T cell therapy.

Presenters at our single-cell symposiums discussed the future of immunotherapies:

  • Mass General Cancer Center’s Marcela Maus described the use of IsoPlexis’ technology in next generation CAR-T constructs.
  • Chelsea Xue of Takeda Pharmaceuticals reviewed CAR-T quality control and characterization. Xue discussed the work she published in the Journal for ImmunoTherapy of Cancer (JITC), where she used IsoPlexis’ technology to characterize the polyfunctionality of immune cell donors used in the creation of CAR-T products for adoptive cell therapy.
  • Matthew Davidson and Martin Kramer from Sanofi Genzyme teamed up to tackle the topic of macrophage and next generation applications. They described how they used single cell cytokine profiling to begin to characterize the polyfunctionality of non-classical monocytes from patient blood.

This Single-Cell Functional Biomarker Symposium series proved to be an educational venue where our partners could share impressive data generated and published through IsoPlexis’ uniquely correlative single-cell detection platform to accelerate the fight against cancer and a range of the world’s toughest diseases. We are looking forward to hosting more of these collaborative and inspiring events soon and we hope to see you there!

Until then, remember to request a seminar if you’d like more information about the growing impact of polyfunctionality and IsoPlexis’ work in immunotherapy!

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