Immune-Cell Numbers Predict Response to Combination Immunotherapy in Melanoma

According to a new study conducted by researchers and clinicians at the University of California, San Francisco (UCSF), an abundance of certain white blood cells present in tumors could be the answer to predicting a patient’s response to immunotherapy.

The study, published on July 20, 2017 in the Journal of Clinical Investigation (JCI) Insights, evaluated tumor samples from 102 patients with melanoma and measured the percentage of a specific subset of immune cells that had infiltrated tumors. Study results showed that patients with lower levels of a type of immune cell called “partially exhausted cytotoxic T lymphocytes” (peCTLs) in their tumors benefited the most from a combination of two immunotherapies.

The findings from this study build upon a previous publication, also led by UCSF researchers, demonstrating that a novel predictive biomarker could identify patients likely to respond to anti-PD-1 checkpoint inhibitor therapies, whereby a high frequency of tumor-infiltrating T cells expressing both CTLA-4 and PD-1 proteins on their cell surface, correlated with patient responses. In the new report, researchers continued to study this peCTL population in pre- treatment tumor biopsies and found that patients with high levels of peCTLs in their tumors still benefitted from the anti-PD-1 monotherapy treatment. By comparison, patients with low levels of peCTLs in their tumors benefitted from an immunotherapy combination.

Improving Response Rates with OncoSec’s ImmunoPulse® IL-12

Data from the JCI Insights study shows that only 5.6% of patients with low peCTL responded to anti-PD-1 alone. In combination with anti-CTLA-4, the response rate improved to 35%. “At OncoSec, we believe that our lead product candidate, ImmunoPulse® IL-12, may improve this response rate even further, said OncoSec President and CEO, Punit Dhillon.

In preliminary studies, OncoSec has shown that ImmunoPulse® IL-12, in combination with anti- PD-1, can yield objective responses in patients with low frequencies of peCTL. Interim data from a phase II study, led by UCSF Principal Investigator Dr. Alain Algazi, showed a 48% best overall response rate from the combination of ImmunoPulse® IL-12 with pembrolizumab in the low peCTL population.

“We believe this combination melanoma trial is the first clinical trial to use this T cell biomarker to evaluate the clinical response of patients with low frequency of peCTL. To date, 48% of the patients evaluable in the interim data of our study showed partial or complete response to the combination”, continued Mr. Dhillon. “These results continue to provide evidence that ImmunoPulse® IL-12, in combination with anti-PD-1 therapies, can improve response rates in advanced melanoma. We believe that these new results reinforce the relevance of the clinical data we presented in this difficult-to-target population, namely those unlikely to respond to anti-PD-1 monotherapy. The data from this study also further validates the approach we have taken in our upcoming PISCES trial; to treat patients that fail to respond to anti-PD-1 therapy alone.”

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