التفاصيل البيبلوغرافية
| العنوان: |
Anti-KIT Monoclonal Antibody Treatment Enhances the Antitumor Activity of Immune Checkpoint Inhibitors by Reversing Tumor-Induced Immunosuppression |
| المؤلفون: |
Lori Lopresti-Morrow, Theresa LaVallee, Andrew Garton, E. Sergio Trombetta, Shannon Pankratz, Linda Crew, Neal Janson, Richard Gedrich, Scott Seibel, Sreekala Mandiyan |
| المصدر: |
Molecular cancer therapeutics. 16(4) |
| سنة النشر: |
2016 |
| مصطلحات موضوعية: |
0301 basic medicine, CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Cancer Research, medicine.drug_class, Population, Programmed Cell Death 1 Receptor, CD8-Positive T-Lymphocytes, Monoclonal antibody, Receptor tyrosine kinase, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Cell Line, Tumor, medicine, Animals, Humans, CTLA-4 Antigen, Phosphorylation, Cytotoxicity, education, Immunosuppression Therapy, education.field_of_study, Innate immune system, biology, Myeloid-Derived Suppressor Cells, Antibodies, Monoclonal, Drug Synergism, Cell Cycle Checkpoints, Xenograft Model Antitumor Assays, Proto-Oncogene Proteins c-kit, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Immunology, Colonic Neoplasms, Cancer research, biology.protein, Antibody, Tyrosine kinase |
| الوصف: |
The receptor tyrosine kinase KIT is an established oncogenic driver of tumor growth in certain tumor types, including gastrointestinal stromal tumors, in which constitutively active mutant forms of KIT represent an actionable target for small-molecule tyrosine kinase inhibitors. There is also considerable potential for KIT to influence tumor growth indirectly based on its expression and function in cell types of the innate immune system, most notably mast cells. We have evaluated syngeneic mouse tumor models for antitumor effects of an inhibitory KIT mAb, dosed either alone or in combination with immune checkpoint inhibitors. Anti-KIT mAb treatment enhanced the antitumor activity of anti–CTLA-4 and anti–PD-1 mAbs, and promoted immune responses by selectively reducing the immunosuppressive monocytic myeloid-derived suppressor cell population and by restoring CD8+ and CD4+ T-cell populations to levels observed in naïve mice. These data provide a rationale for clinical investigation of the human KIT-specific mAb KTN0158 in novel immuno-oncology combinations with immune checkpoint inhibitors and other immunotherapeutic agents across a range of tumor types. Mol Cancer Ther; 16(4); 671–80. ©2017 AACR. |
| تدمد: |
1538-8514 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::562d1285cd08a95537e834b8d69e882f
https://pubmed.ncbi.nlm.nih.gov/28138031 |
| رقم الانضمام: |
edsair.doi.dedup.....562d1285cd08a95537e834b8d69e882f |
| قاعدة البيانات: |
OpenAIRE |