Trained immunity-promoting nanobiologic therapy suppresses tumor growth and potentiates checkpoint inhibition Journal Article
| Authors: | Priem, B.; van Leent, M. M. T.; Teunissen, A. J. P.; Sofias, A. M.; Mourits, V. P.; Willemsen, L.; Klein, E. D.; Oosterwijk, R. S.; Meerwaldt, A. E.; Munitz, J.; Prévot, G.; Vera Verschuur, A.; Nauta, S. A.; van Leeuwen, E. M.; Fisher, E. L.; de Jong, K. A. M.; Zhao, Y.; Toner, Y. C.; Soultanidis, G.; Calcagno, C.; Bomans, P. H. H.; Friedrich, H.; Sommerdijk, N.; Reiner, T.; Duivenvoorden, R.; Zupančič, E.; Di Martino, J. S.; Kluza, E.; Rashidian, M.; Ploegh, H. L.; Dijkhuizen, R. M.; Hak, S.; Pérez-Medina, C.; Bravo-Cordero, J. J.; de Winther, M. P. J.; Joosten, L. A. B.; van Elsas, A.; Fayad, Z. A.; Rialdi, A.; Torre, D.; Guccione, E.; Ochando, J.; Netea, M. G.; Griffioen, A. W.; Mulder, W. J. M. |
| Article Title: | Trained immunity-promoting nanobiologic therapy suppresses tumor growth and potentiates checkpoint inhibition |
| Abstract: | 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. © 2020 Elsevier Inc. A bone marrow targeted nanobiologic platform that is designed to elicit trained immunity responses has the ability to reduce tumor growth and augment immune checkpoint blockade. © 2020 Elsevier Inc. |
| Keywords: | melanoma; immunotherapy; nanomedicine; innate immunity; nanotechnology; myeloid cells; cancer; checkpoint inhibitors; trained immunity; nanobiologics |
| Journal Title: | Cell |
| Volume: | 183 |
| Issue: | 3 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2020-10-29 |
| Start Page: | 786 |
| End Page: | 801.e19 |
| Language: | English |
| DOI: | 10.1016/j.cell.2020.09.059 |
| PUBMED: | 33125893 |
| PROVIDER: | scopus |
| PMCID: | PMC8074872 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
