TY - JOUR
T1 - Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition
AU - Priem, Bram
AU - van Leent, Mandy M.T.
AU - Teunissen, Abraham J.P.
AU - Sofias, Alexandros Marios
AU - Mourits, Vera P.
AU - Willemsen, Lisa
AU - Klein, Emma D.
AU - Oosterwijk, Roderick S.
AU - Meerwaldt, Anu E.
AU - Munitz, Jazz
AU - Prévot, Geoffrey
AU - Vera Verschuur, Anna
AU - Nauta, Sheqouia A.
AU - van Leeuwen, Esther M.
AU - Fisher, Elizabeth L.
AU - de Jong, Karen A.M.
AU - Zhao, Yiming
AU - Toner, Yohana C.
AU - Soultanidis, Georgios
AU - Calcagno, Claudia
AU - Bomans, Paul H.H.
AU - Friedrich, Heiner
AU - Sommerdijk, Nico
AU - Reiner, Thomas
AU - Duivenvoorden, Raphaël
AU - Zupančič, Eva
AU - Di Martino, Julie S.
AU - Kluza, Ewelina
AU - Rashidian, Mohammad
AU - Ploegh, Hidde L.
AU - Dijkhuizen, Rick M.
AU - Hak, Sjoerd
AU - Pérez-Medina, Carlos
AU - Bravo-Cordero, Jose Javier
AU - de Winther, Menno P.J.
AU - Joosten, Leo A.B.
AU - van Elsas, Andrea
AU - Fayad, Zahi A.
AU - Rialdi, Alexander
AU - Torre, Denis
AU - Guccione, Ernesto
AU - Ochando, Jordi
AU - Netea, Mihai G.
AU - Griffioen, Arjan W.
AU - Mulder, Willem J.M.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/10/29
Y1 - 2020/10/29
N2 - 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. Furthermore, MTP10-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to 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 elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.
AB - 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. Furthermore, MTP10-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to 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 elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.
KW - cancer
KW - checkpoint inhibitors
KW - immunotherapy
KW - innate immunity
KW - melanoma
KW - myeloid cells
KW - nanobiologics
KW - nanomedicine
KW - nanotechnology
KW - trained immunity
UR - http://www.scopus.com/inward/record.url?scp=85094983590&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.09.059
DO - 10.1016/j.cell.2020.09.059
M3 - Article
C2 - 33125893
AN - SCOPUS:85094983590
SN - 0092-8674
VL - 183
SP - 786-801.e19
JO - Cell
JF - Cell
IS - 3
ER -