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While advancements in cancer therapeutics are occurring at breakneck speed, one thing remains certain: tumor cells are tricky. To evade immune detection and T cell–mediated killing, a tumor cell expresses an immune checkpoint ligand on its surface which binds to its respective partner on T cells, shutting off immune-mediated tumor, killing pathways. Immune checkpoint inhibitor therapies block this process from occurring, thus allowing T cells to kill tumor cells.

Immune checkpoint inhibitor therapies have revolutionized cancer treatments, improving patient survival rates in a number of cancers, including metastatic melanoma. However, these therapies may not produce durable responses in all patients.

Existing treatment options include those targeting intracellular pathways such as BRAF inhibition, a mechanism by which melanoma cells have shown to develop treatment resistance; chemotherapy; adoptive T cell therapy; and immune checkpoint therapy. Immune checkpoint therapies are especially promising for those with late-stage melanoma.

IsoPlexis’ Blood-Based Biomarker Predicts Response and Progression-Free Survival

In a study published in the Journal of Clinical Oncology, researchers explored the efficacy of a novel checkpoint inhibitor in late-stage melanoma patients in a Phase II clinical trial.

To be eligible for the novel therapy, patients must have been diagnosed and confirmed to have stage III or stage IV melanoma with no history of prior treatment. Patients who showed a reduction in tumor size were considered to have either a partial response or a complete response.

To identify a biomarker for patient response, researchers evaluated both patient tumor and blood samples. The study identified high IFN-g gene expression, high tumor-infiltrating CD8+ T cells, high CD74, and high HLA-E as positive indications of high objective response rate.

Using IsoPlexis’ unique technology, researchers identified a blood-based biomarker which predicted progression-free survival in melanoma patients. The researchers found that the week 1 polyfunctional strength difference (PSD), defined by the difference in PSI between cycle 1 day 8 and baseline, predicted eventual response to the novel treatment in first-line metastatic melanoma. Importantly, progression-free survival curves were stratified by PSD. This underscores the potential of single-cell polyfunctionality as a predictive biomarker that positively correlates with patient response.

Conclusion

This study demonstrates the efficacy of a novel combination immunotherapy for the treatment of metastatic melanoma with IsoPlexis’ polyfunctional strength index serving as a key metric that effectively predicted overall patient response rate.

The predictive blood-based biomarker identified by IsoPlexis’ platform enables researchers to evaluate patient response to the novel therapy much earlier than was previously possible with traditional technologies. IsoPlexis’ unique functional biology accelerates insights into difficult-to-treat cancers such as metastatic melanomas, identifying treatments associated with a durable response in patients.

 

Adi Diab, et al. Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma. Journal of Cllinical Oncology 2021.

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