Discovery of a Novel Microtubule Targeting Agent as an Adjuvant for Cancer Immunotherapy
المؤلفون المشاركون
Hayashi, Tomoko
Yao, Shiyin
Chan, Michael
Cottam, Howard B.
Lao, Fitzgerald
Carson, Dennis A.
Sato-Kaneko, Fumi
Wang, Xiaodong
Hosoya, Tadashi
Shukla, Nikunj M.
Corr, Maripat
Messer, K.
Pu, M.
المصدر
العدد
المجلد 2018، العدد 2018 (31 ديسمبر/كانون الأول 2018)، ص ص. 1-13، 13ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2018-10-10
دولة النشر
مصر
عدد الصفحات
13
التخصصات الرئيسية
الملخص EN
For an activating immunotherapy such as adjuvants, a compound that can prolong immune stimulation may enhance efficacy.
We leveraged data from two prior high throughput screens with NF-κB and interferon reporter cell lines to identify 4H-chromene-3-carbonitriles as a class of compounds that prolonged activation in both screens.
We repurchased 23 of the most promising candidates.
Out of these compounds we found #1 to be the most effective agent in stimulating the release of cytokines and chemokines from immune cells, including murine primary bone marrow derived dendritic cells.
Mechanistically, #1 inhibited tubulin polymerization, and its effect on immune cell activation was abolished in cells mutated in the beta-tubulin gene (TUBB) encoding the site where colchicine binds.
Treatment with #1 resulted in mitochondrial depolarization followed by mitogen-activated protein kinase activation.
Because tubulin polymerization modulating agents have been used for chemotherapy to treat malignancy and #1 activated cytokine responses, we hypothesized that #1 could be effective for cancer immunotherapy.
Intratumoral injection of #1 delayed tumor growth in a murine syngeneic model of head and neck cancer.
When combined with PD-1 blockade, tumor growth slowed in the injected tumor nodule and there was an abscopal effect in an uninjected nodule on the contralateral flank, suggesting central antitumor immune activation.
Thus, we identified a new class of tubulin depolymerizing agent that acts as both an innate and an adaptive immune activating agent and that limits solid tumor growth when used concurrently with a checkpoint inhibitor.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Sato-Kaneko, Fumi& Wang, Xiaodong& Yao, Shiyin& Hosoya, Tadashi& Lao, Fitzgerald& Messer, K.…[et al.]. 2018. Discovery of a Novel Microtubule Targeting Agent as an Adjuvant for Cancer Immunotherapy. BioMed Research International،Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1128883
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Sato-Kaneko, Fumi…[et al.]. Discovery of a Novel Microtubule Targeting Agent as an Adjuvant for Cancer Immunotherapy. BioMed Research International No. 2018 (2018), pp.1-13.
https://search.emarefa.net/detail/BIM-1128883
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Sato-Kaneko, Fumi& Wang, Xiaodong& Yao, Shiyin& Hosoya, Tadashi& Lao, Fitzgerald& Messer, K.…[et al.]. Discovery of a Novel Microtubule Targeting Agent as an Adjuvant for Cancer Immunotherapy. BioMed Research International. 2018. Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1128883
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1128883
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر