納米生物療法在腫瘤免疫中的應用
作者：
小柯機器人發布時間：2020/10/31 19:35:14
美國西奈山伊坎醫學院Willem J.M. Mulder團隊取得最新進展。他們揭示馴化的免疫增強的納米生物療法可抑制腫瘤生長並增強檢查點抑制作用。該研究於2020年10月29日發表於國際一流學術期刊《細胞》雜誌上。
他們開發了一種專門設計用於誘導馴化過的免疫力的骨髓航空納米生物學平臺。他們在B16F10小鼠黑色素瘤模型中建立了主要候選藥物MTP10-HDL的有效抗腫瘤能力。這些抗腫瘤作用歸因於骨髓中多能祖細胞的表觀遺傳學重組，導致馴化的免疫誘導的骨髓生成，從而克服了免疫抑制的腫瘤微環境。
此外，MTP10-HDL納米療法在這種抗PD-1和CTLA-4治療的黑色素瘤模型中增強了檢查點抑制。最後，他們確定了MTP10-HDL在非人類靈長類動物中的良好生物分布和安全性。
總而言之，他們表明，合理設計的納米生物製劑既可以作為單一療法，也可以與檢查點抑制劑藥物聯合使用，從而可以提高馴化的免疫力並引起持久的抗腫瘤反應。
研究人員表示，馴化的免疫是髓樣細胞的一種功能狀態，已被提出作為引人注目的免疫腫瘤靶標。它的有效誘導需要骨髓祖細胞直接參與骨髓中。
附：英文原文
Title: Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition
Author: Bram Priem, Mandy M.T. van Leent, Abraham J.P. Teunissen, Alexandros Marios Sofias, Vera P. Mourits, Lisa Willemsen, Emma D. Klein, Roderick S. Oosterwijk, Anu E. Meerwaldt, Jazz Munitz, Geoffrey Prévot, Anna Vera Verschuur, Sheqouia A. Nauta, Esther M. van Leeuwen, Elizabeth L. Fisher, Karen A.M. de Jong, Yiming Zhao, Yohana C. Toner, Georgios Soultanidis, Claudia Calcagno, Paul H.H. Bomans, Heiner Friedrich, Nico Sommerdijk, Thomas Reiner, Raphal Duivenvoorden, Eva Zupani, Julie S. Di Martino, Ewelina Kluza, Mohammad Rashidian, Hidde L. Ploegh, Rick M. Dijkhuizen, Sjoerd Hak, Carlos Pérez-Medina, Jose Javier Bravo-Cordero, Menno P.J. de Winther, Leo A.B. Joosten, Andrea van Elsas, Zahi A. Fayad, Alexander Rialdi, Denis Torre, Ernesto Guccione, Jordi Ochando, Mihai G. Netea, Arjan W. Griffioen, Willem J.M. Mulder
Issue&Volume: 2020/10/29
Abstract: Trained immunity, a functional state of myeloid cells, has been proposed as a compellingimmune-oncological target. Its efficient induction requires direct engagement of myeloidprogenitors in the bone marrow. For this purpose, we developed a bone marrow-avidnanobiologic platform designed specifically to induce trained immunity. We establishedthe potent anti-tumor capabilities of our lead candidate MTP10-HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trainedimmunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitorsin the bone marrow, which overcomes the immunosuppressive tumor microenvironment.Furthermore, MTP10-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractoryto anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP10-HDL’s favorable biodistribution and safety profile in non-human primates. In conclusion,we show that rationally designed nanobiologics can promote trained immunity and elicita durable anti-tumor response either as a monotherapy or in combination with checkpointinhibitor drugs.
DOI: 10.1016/j.cell.2020.09.059
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31300-3
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216