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Myeloid-Derived Suppressor Cells in Checkpoint Protein Inhibition for Melanoma

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New York University New York United States

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Myeloid-derived suppressor cells MDSC are one of the major negative regulators of immune responses in cancer closely associated with negative outcome of PD1 therapy in metastatic melanoma. TRAIL-R DR5 is selectively up- regulated on MDSC. The goal of this study is to test the hypothesis that agonistic TRAIL-DR5 antibody DS-8273a will be well tolerated and augment the clinical efficacy of PD-1 blocking antibody nivolumab by impacting on MDSC. DS-8372a at low doses 4 and 8 mgkg was well tolerated with 2 excellent responses in 6 patients and one mixed response it did not affect populations of MDSC or other myeloid and lymphoid cells, but monocytic MDSC function was augmented. In the first 4 patients we evaluated the response of T cells to melanoma derived pool of overlapping peptides in IFN- ELISPOT assay. In one patient we observed substantial increase in the response to peptides after 3 cycles of treatment. These results are preliminary. Moreover, the dose of antibody was very low to expect substantial responses. We anticipate that next two doses 16 mgkg and24 mgkg with escalation occurring early in October will provide more clear data.

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Technical Report,01 Sep 2016,31 Aug 2017



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