Myeloid-Derived Suppressor Cells in Checkpoint Protein Inhibition for Melanoma
Abstract
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 mg/kg) 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 mg/kg and24 mg/kg) with escalation occurring early in October will provide more clear data.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2017
- Accession Number
- AD1046087
Entities
People
- Jeffrey Weber
Organizations
- New York University