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Study Published in Nature Suggests immunoSEQ Assay May Be Used to Predict Response to anti-PD-1 Therapy for Melanoma

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Adaptive Biotechnologies, a pioneer in leveraging Next Generation Sequencing (NGS) to profile T- and B-cell receptors, recently reported that the immunoSEQ Assay was able to help identify patients with metastatic melanoma who would be most likely to respond to treatment with pembrolizumab (an anti-PD-1 therapy), according to a study published in Nature.

The multi-parameter two-year study, led by Drs. Paul Tumeh and Antoni Ribas of the UCLA Jonsson Comprehensive Cancer Center, validated the hypothesis that an immune response depicted by a less diverse (more clonal) immune repertoire prior to treatment, does correlate with clinical response (P=0.004) to treatment with pembrolizumab, the first PD1 inhibitor to receive FDA approval earlier in 2014. In addition, more than ten times as many T-cell clones expanded after therapy in the responders than in those who progressed on treatment.

“Patients who respond to anti-PD1 therapy had their immune system ready to attack the cancer, but it was being held back by PD-1,” said Ribas. “By releasing this break, the patients’ immune system can mount an even stronger attack on the cancer anywhere in the body. The immunoSEQ Assay confirmed both the existing immune system readiness prior to treatment and the quantitative validation of the stronger presence of T-cells post-treatment in the responders.”

In the study, Adaptive’s immunoSEQ Assay was used to sequence the T cell repertoire within the tumor before treatment to assess characteristics of the adaptive immune response to the tumor that indicate a higher likelihood of response to pembrolizumab, and after treatment to detect differences in the resultant immune repertoire between responders and non-responders. Expression levels of PD-1/PDL-1 and presence of T-cell antigen receptors (TCRs) were hypothesized to differ between responders and non-responders both prior to and after treatment. In samples from 46 patients, using quantitative immunohistochemistry and quantitative multiplex immunofluourescence, the study reports that higher levels of PD-1/PDL-1 are more prevalent in responders, and high-density effector T cells can be found in the tumors in the response group, suggesting a specific immune response to the tumor.

Harlan Robins, founder of Adaptive Biotechnologies and study author, said, “Adaptive is honored to partake in this critical biomarker study with UCLA, and is committed to using our TCR sequencing assay to enhance our ability to predict responders to PD1 inhibitors and other targeted cancer immunotherapies that leverage the body’s own ability to fight cancer. It appears to be a consistent finding that having an immune system that is ready to attack is key to response to many immunotherapies.” 

Source: PR Newswire