دورية أكاديمية
Myeloid-Derived Suppressor Cells in Checkpoint Protein Inhibition for Melanoma
| العنوان: | Myeloid-Derived Suppressor Cells in Checkpoint Protein Inhibition for Melanoma |
|---|---|
| المؤلفون: | Weber, Jeffrey |
| المساهمون: | New York University New York United States |
| سنة النشر: | 2017 |
| المجموعة: | Defense Technical Information Center: DTIC Technical Reports database |
| مصطلحات موضوعية: | Medicine and Medical Research, Pharmacology, Biochemistry, SKIN CANCER, proteins, inhibition, antibodies, peptides, POLYMORPHONUCLEAR LEUKOCYTES, endoplasmic reticulum, apoptosis, t lymphocytes, antigens, SURVIVAL, MYELOID CELLS, toxicity, mdsc (Myeloid derived suppressor cells), TNR-related apoptosis induced ligand-receptors, melanoma, DS-8372a, inducible nitric oxide synthetase, tgf-B (transforming growth factor beta), major histocompatibility complex, ros (reactive oxygen species), peroxynitrate, quantitative reverse transcription polymerase chain reaction, inositol-requiring enzyme 1, x-box binding protein-1, osteoprotegerin |
| الوصف: | 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. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://www.dtic.mil/docs/citations/AD1046087Test |
| الإتاحة: | http://www.dtic.mil/docs/citations/AD1046087Test http://oai.dtic.mil/oai/oai?&verb=getRecord&metadataPrefix=html&identifier=AD1046087Test |
| حقوق: | Approved For Public Release |
| رقم الانضمام: | edsbas.829385CF |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |