Checkpoint Immunotherapy in Solid Tumor Is Evolving: Advancing Cellular Fitness & Precision Medicine with IsoPlexis’ Platform

Checkpoint immunotherapy development continues to grow at an incredible rate, with two of the three largest selling oncology drugs being checkpoint-based immunotherapies (Opdivo [nivolumab] and Keytruda [pembrolizumab]).

As of 2018, about 2250 clinical trials in immunotherapy involved checkpoint therapy. Many of the most cutting-edge immune-oncology trials have become much more complex, combining checkpoint inhibitors with a variety of small molecules, agonists, vaccines, and multiple checkpoint therapies. This presents a competitive atmosphere for deciding which mono and combinatorial therapies will be of highest utility in various indications, and also a complex environment for understanding both mechanistically and biomarker-wise how these therapies can be used in a precise manner for the right patient at the right time.

More Predictive & Higher Resolution T Cell Immune Fitness Profiling at the Single-Cell Cytokine Level

IsoPlexis has begun to help unravel these questions in complex checkpoint and combination immunotherapies over the last few years. Researchers have now used IsoCode technology for profiling T cell function from the tumor, bone marrow, and blood of a variety of patients in a number of published and public trials. The results have demonstrated how IsoPlexis’ new resolution into the cytokine signatures of single cells points to a novel ability to stratify complex patient responses in combination checkpoint therapy and offers a glimpse into the future of understanding mechanism and personalized medicine in these complex immunotherapies. A few examples include:

• BMS’ Ipi/Nivo (CTLA4/Anti-PD1) therapy, in melanoma trial with Yale: Here, researchers used IsoPlexis’ single-cell cytokine detection system to analyze tumor infiltrating lymphycytes (TILs) used in their Ipi/Nivo therapy trial. PSI suggested that highly polyfunctional TILs, producing multiple cytokines per single cell, could be a potential biomarker in predicting outcome of melanoma patients treated by checkpoint therapies.
• Merck’s Pembro (Anti-PD1) therapy, in lung adenocarcinoma trial with WVU Cancer Institute: Researchers used IsoPlexis’ single-cell platform to reach a similar conclusion by looking at T cell functional response in the blood: "Preliminary data nominates PSI as potential predictive biomarker of CPI response, linking single-cell cytokine profiling to clinical outcome, esp. in a MET-amplified lung adenocarcinoma."
  • Polyfunctionality, the ability of single T cells to produce highly multiplexed cytokines, was increased post-treatment, which correlated with response in a specific cytokine signature. This is a unique metric on IsoPlexis’ single-cell true secreted protein platform.
• BMS’ Nivo (Anti-PD1) with Azacytidine therapy in AML with MD Anderson: Researchers from MD Anderson used the IsoPlexis cytokine detection system to analyze bone marrow cells from AML patients treated with their Nivo/Aza therapy. All responding patients had a PSI>10 with a significant correlation of p = 0.0018. Dr. Naval Daver from MD Anderson said, "…this could just be a marker [indicating] that these patients have preserved immune function and will have a better chance of response to other cytotoxic therapies."

Figure 2

Advancing Precision Cellular Fitness Using Single T Cell Cytokine Detection in Checkpoint Immune Monitoring in Solid Tumor

Researchers are using IsoPlexis’ next generation platform to analyze the true functional proteomic single-cell biology of their patients and stratify responders from non-responders to therapy in checkpoint therapy.

These highly functional cells that researchers are using to differentiate and understand response are unique to IsoPlexis’ system and cannot be seen on ELISA and flow cytometry-based platforms, or in RNA. See why this unique Single-Cell Biology works and makes sense in its ability to capture immune fitness here.

We also invite you to take a deeper look at some of our case studies and see how IsoPlexis’ platform is helping to make a difference in accelerating decision making in the development and biomarker strategy of their most complex solid tumor focused checkpoint therapies.