Accession Number : AD1046087


Title :   Myeloid-Derived Suppressor Cells in Checkpoint Protein Inhibition for Melanoma


Descriptive Note : Technical Report,01 Sep 2016,31 Aug 2017


Corporate Author : New York University New York United States


Personal Author(s) : Weber, Jeffrey


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1046087.pdf


Report Date : 01 Sep 2017


Pagination or Media Count : 29


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.


Descriptors :   SKIN CANCER , proteins , inhibition , antibodies , peptides , POLYMORPHONUCLEAR LEUKOCYTES , endoplasmic reticulum , apoptosis , t lymphocytes , antigens , SURVIVAL , MYELOID CELLS , toxicity


Subject Categories : Medicine and Medical Research
      Pharmacology
      Biochemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE