Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition

Priem, Bram; Leent, Mandy M. T. van; Teunissen, Abraham J. P.; Sofias, Alexandros Marios; Mourits, Vera P.; Willemsen, Lisa; Klein, Emma D.; Oosterwijk, Roderick S.; Meerwaldt, Anu E.; Munitz, Jazz; Prévot, Geoffrey; Verschuur, Anna Vera D; Nauta, Sheqouia A.; Leeuwen, Esther M. van; Fisher, Elizabeth L.; Jong, Karen A.M. de; Zhao, Yiming; Toner, Yohana C.; Soultanidis, Georgios; Calcagno, Claudia; Bomans, Paul H. H.; Friedrich, Heiner; Sommerdijk, Nico A. J. M.; Reiner, Thomas; Duivenvoorden, Raphaël; Zupančič, Eva; Martino, Julie Di; Kluza, Ewelina; Rashidian, Mohammad; Ploegh, Hidde L.; Dijkhuizen, Rick M.; Hak, Sjoerd; Pérez-Medina, Carlos; Bravo‐Cordero, Jose Javier; Winther, Menno P.J. de; Joosten, Leo A. B.; Elsas, Andrea van; Fayad, Zahi A.; Rialdi, Alexander; Torre, Denis; Guccione, Ernesto; Ochando, Jordi; Netea, Mihai G.; Griffioen, Arjan W.; Mulder, Willem J. M.

doi:10.1016/j.cell.2020.09.059

Cited by 130 publications

(107 citation statements)

References 59 publications

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“…Therefore, we subsequently focused on the development and evaluation of the 20-, 35-, and 65-nm-sized formulations. Cryogenic transmission electron microscopy (cryo-TEM) analyses uncovered the 20-nm nanobiologic as circular shapes, which match the discoidal morphology we previously observed by TEM and cryo-TEM for similar formulations (7,12). In contrast, the 35-and 65-nm nanobiologics have uniform contrast and a seemingly spherical shape as a result of their tricaprylin core (Fig.…”

Section: Developing Nanobiologics With High Affinity For Myeloid Cellssupporting

confidence: 80%

“…The relation between promoiety structure and prodrug in vivo behavior will be of special interest. Although our current study used drugs that induce immunological tolerance, similar platforms can be used to initiate other types of innate immune responses (12). Producing these immunostimulatory nanotherapeutics in a modular fashion could greatly benefit treating a broad variety of diseases, including cancer or coronavirus disease 2019 (COVID-19) (25,26).…”

Section: Discussionmentioning

confidence: 99%

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A modular approach toward producing nanotherapeutics targeting the innate immune system

et al. 2021

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Immunotherapies controlling the adaptive immune system are firmly established, but regulating the innate immune system remains much less explored. The intrinsic interactions between nanoparticles and phagocytic myeloid cells make these materials especially suited for engaging the innate immune system. However, developing nanotherapeutics is an elaborate process. Here, we demonstrate a modular approach that facilitates efficiently incorporating a broad variety of drugs in a nanobiologic platform. Using a microfluidic formulation strategy, we produced apolipoprotein A1–based nanobiologics with favorable innate immune system–engaging properties as evaluated by in vivo screening. Subsequently, rapamycin and three small-molecule inhibitors were derivatized with lipophilic promoieties, ensuring their seamless incorporation and efficient retention in nanobiologics. A short regimen of intravenously administered rapamycin-loaded nanobiologics (mTORi-NBs) significantly prolonged allograft survival in a heart transplantation mouse model. Last, we studied mTORi-NB biodistribution in nonhuman primates by PET/MR imaging and evaluated its safety, paving the way for clinical translation.

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Section: Developing Nanobiologics With High Affinity For Myeloid Cellssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

A modular approach toward producing nanotherapeutics targeting the innate immune system

et al. 2021

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“…Trained immunity of bone marrow progenitors induced by MTP-HDL lowered TAM numbers and suppressed tumor growth. Moreover, the combination of MTP-HDL with either anti-PD-1, anti-CTLA-4, or both anti-PD-1 + anti-CTLA-4 ICB further enhanced the anti-tumor effect of MTP-HDL therapy [251]. Furthermore, the combination of training agents with ICB and therapies known to induce immunogenic cell death may be beneficial.…”

Section: Macrophages and Trained Immunity: A Novel Therapeutic Target?mentioning

confidence: 99%

“…Whether acquisition of trained immunity promotes tumor suppressive phenotypes in macrophages is currently under investigation. Recently, Priem and colleagues developed a nanobiological therapy, MTP-HDL, that demonstrated remarkable anti-tumor efficacy by potentiating checkpoint inhibition in a mouse model of melanoma [251]. Trained immunity of bone marrow progenitors induced by MTP-HDL lowered TAM numbers and suppressed tumor growth.…”

Section: Macrophages and Trained Immunity: A Novel Therapeutic Target?mentioning

confidence: 99%

Tissue-Resident and Recruited Macrophages in Primary Tumor and Metastatic Microenvironments: Potential Targets in Cancer Therapy

Cotechini

Atallah

Grossman

2021

Cells

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Macrophages within solid tumors and metastatic sites are heterogenous populations with different developmental origins and substantially contribute to tumor progression. A number of tumor-promoting phenotypes associated with both tumor- and metastasis-associated macrophages are similar to innate programs of embryonic-derived tissue-resident macrophages. In contrast to recruited macrophages originating from marrow precursors, tissue-resident macrophages are seeded before birth and function to coordinate tissue remodeling and maintain tissue integrity and homeostasis. Both recruited and tissue-resident macrophage populations contribute to tumor growth and metastasis and are important mediators of resistance to chemotherapy, radiation therapy, and immune checkpoint blockade. Thus, targeting various macrophage populations and their tumor-promoting phenotypes holds therapeutic promise. Here, we discuss various macrophage populations as regulators of tumor progression, immunity, and immunotherapy. We provide an overview of macrophage targeting strategies, including therapeutics designed to induce macrophage depletion, impair recruitment, and induce repolarization. We also provide a perspective on the therapeutic potential for macrophage-specific acquisition of trained immunity as an anti-cancer agent and discuss the therapeutic potential of exploiting macrophages and their traits to reduce tumor burden.

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“…Inducing the so-called 'trained immunity' demonstrated antitumor efficacy and potentiated checkpoint inhibition immunotherapy in a preclinical study. 2 The biologic MTP 10 -HDL combines bone marrow-targeted nanomaterial with a drug that epigenetically modifies myeloid progenitor cells, leading to reversal of the immunosuppressive nature of tumor microenvironment.…”

Section: Bone Marrow-targeting Nanobiologic Might Improve Checkpointmentioning

confidence: 99%

Human Vaccines & Immunotherapeutics: news

2020

Human Vaccines & Immunotherapeutics

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Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition

Cited by 130 publications

References 59 publications

A modular approach toward producing nanotherapeutics targeting the innate immune system

A modular approach toward producing nanotherapeutics targeting the innate immune system

Tissue-Resident and Recruited Macrophages in Primary Tumor and Metastatic Microenvironments: Potential Targets in Cancer Therapy

Human Vaccines & Immunotherapeutics: news

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