Published in Nature Medicine: Utilizing IsoPlexis’ Single-Cell Proteomics and Product Quality Metrics in a Phase I Trial of TIL treatment for Metastatic Lung Cancer

Limitations in Current Treatment Landscape for NSCLCs

PD-1 immune-checkpoint inhibitors have made significant advancements in treating metastatic lung cancer, but still have a long way to go. Even when coupled with chemotherapy, patients may continue to experience cancer progression. While researchers continue to discover new immune checkpoint combinations, clinical results have been mixed. 1 Treatment options for non-small cell lung cancers (NSCLCs) can be especially challenging due to their shortage of activated, tumor specific T cells. To combat this, researchers are using adoptive cell therapy (ACT) to provide patients with a large influx of T cells with tumor specificity. Tumor-infiltrating lymphocytes (TILs) that are cultured from a patient’s tumor have shown durable responses in a subset of patients with metastatic melanoma. Given this success, researchers at Duke University and Moffitt have conducted a single-arm open-label Phase I trial of TILs administered with nivolumab in 20 patients with advanced NSCLC following initial progression on nivolumab monotherapy.1 The team recently published their work in Nature Medicine.

In this study, researchers expanded autologous TILs from tumors cultured with interleukin-2. Patients received cyclophosphamide and fludarabine lymphodepletin, TIL infusion and interleukin-2, followed by maintenance nivolumab. Out of the 13 patients that could be evaluated, 3 had confirmed responses and 11 had reduction in tumor burden. Two patients achieved complete responses that were ongoing 1.5 years later. The team also detected T cells that recognized multiple types of cancer mutations after TIL treatment and were enriched in responding patients.1

Single-Cell Functional Proteomics Provides Predictive Product Quality Metrics

The team used IsoPlexis’ platform in this work, demonstrating the power of IsoPlexis’ single-cell functional phenotyping, as it provided a predictive metric for potency and persistence in TIL therapies.  In the study, Polyfunctional Strength Index (PSI) was used to measure the ability of single T cells to secrete multiple different cytokines after stimulation. PSI is an indicator of the number of cells capable of secreting multiple types of cytokines, and reflects the ability of a T cell to carry out multiple functions.

“We assessed the polyfunctional strength index (PSI), which is an indicator of the number of cells capable of secreting multiple types of cytokines. As PSI reflects the ability of a T cell to carry out multiple functions, it is recognized as a metric for the potency of cell therapy and for the efficacy of vaccines.”

This is just one example that showcases the power of IsoPlexis’ unique biology, as it helps researchers advance TIL therapies by providing predictive quality metrics. In a previous study with Iovance, IsoPlexis’ technology showed that highly functional TIL subsets correlated with potent anti-tumor response. It’s evident that the IsoPlexis platform fills a critical need in the field, accelerating next-generation therapies.

References

  1. Creelan, B.C., Wang, C., Teer, J.K. et al. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Nat Med 27, 1410–1418 (2021). https://doi.org/10.1038/s41591-021-01462-y
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