IsoPlexis recently attended the 2019 AACR conference, where several institutions presented data obtained on the IsoPlexis platform. Single-cell functional proteomics data is making an impact on research in checkpoint and combination immunotherapies as well as cell therapies. Read on to see highlights from some of the presentations at AACR.
Single-Cell Immune PSI Fitness Correlates to Treatment Number and Overall Survival in Checkpoint Therapy
MD Anderson’s Daver et al. presented “Polyfunctionality determined by single-cell proteomics of bone marrow-derived CD4 T cells from patients with acute myeloid leukemia identifies patients responding to anti-PD-1-based therapy and discovers profound T cell defect in mutant TP53 disease.”
Researchers identified potential predictive biomarkers for acute myeloid leukemia (AML) towards improving immunotherapies and patient immune status. T cells were loaded onto IsoPlexis’ IsoCode Chip and analyzed on the IsoPlexis platform. The study found that newly diagnosed, untreated patients with AML carrying TP53 mutations showed a pronounced decrease in PSI (p = 0.013). All responding patients had a PSI>10 with a significant correlation of p = 0.0018. PSI pre-therapy was a strong predictor of patient response and overall survival in patients treated with this combination therapy and may be used to identify suitable patients for clinical trials.
Accelerating Pre-Clinical Immune Profiling in Triple Checkpoint Blockade
Kaufmann et al. from Tesaro presented “Triple checkpoint blockade targeting PD-1, TIM-3, and LAG-3 reinvigorates ovarian cancer-infiltrating T cells by increasing T cell polyfunctionality and effector function.”
The IsoCode Chip was used to detect and quantify 32+ functional cytokines secreted from live, single cells. IsoPlexis’ novel metric, PSI, which has been associated with improved response to checkpoint inhibition and has correlated with outcome in multiple studies, was then used to characterize combination therapies. The results showed that triple combination treatment was able to significantly increase the PSI of CD4+ and CD8+ TILs by 2.9 and 3.7-fold, respectively (p < 0.001). This data suggests that triple combination checkpoint blockades may be a viable treatment option for ovarian cancer.
Single-Cell PSI and TCR-Seq Correlates in Solid Tumor Patients
Seo et al. at Fred Hutch, other researchers, and IsoPlexis presented “Single-cell polyfunctionality of circulating CD4+ T cells correlates with T cell receptor repertoire diversity of PBMCs, indicating potential synergistic activity and peripheral biomarker predictive of efficacy of intratumor injection of the toll-like receptor 4 agonist G100.”
Researchers used IsoPlexis technology to study the efficacy of engineered cell product and polyfunctional response correlating to TCR diversity in soft tissue sarcomas. It was found that a greater variety of proteins associated with anti-tumor immunity was detected in CD4+ T cells post-treatment. More importantly, the pre-treatment CD4 PSI positively correlated with the TCR diversity of PBMCs (p = 0.0185).
Single-Cell PSI Reveals Upregulation in Neoepitope-Specific Adoptive Cell Therapy
Data generated on the IsoLight was presented by researchers at PACT Pharma in this session “NeoTCR-P1, a novel neoepitope-specific adoptive cell therapy, consists of T cells with ‘younger’ phenotypes that rapidly proliferate and kill target cells upon recognition of cognate antigen.”
Researchers, in developing personalized autologous therapies for solid tumors, found that single cell secretome analysis demonstrated that the NeoTCR-P1 cells were highly polyfunctional. These results indicate that these engineered T cells have the potential to provide substantial clinical benefit to patients with solid tumors.
These are just a few examples of how IsoPlexis’ platform is making an impact in the immunotherapy field. If you’d like more information on how IsoPlexis’ platform can make a difference in your research and immunotherapy development, reach out to speak with a single-cell functional proteomics expert here.