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, Raphaël Duivenvoorden, Eva Zupančič, 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
Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP10 -HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment...
October 29, 2020: Cell