{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T07:05:02Z","timestamp":1768719902179,"version":"3.49.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Council","award":["ERC-2012-StG_20111109"],"award-info":[{"award-number":["ERC-2012-StG_20111109"]}]},{"name":"The Lundbeck Foundation Fellowship"},{"name":"The Novo Foundation Synergy"},{"name":"The Danish Research Council for Independent Research Sapere Aude"},{"name":"Innovation Fund Denmark\u2014Grand Solutions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immunostimulants can be highly effective anti-cancer therapeutics; however, their systemic use is often limited by adverse reactions (AEs). Formulating immunostimulants into nanoparticle systems can potentially alleviate these, but nanoparticle design is key. In previous studies, we encountered anti-nanoparticle reactions with systemically administered PEGylated liposomes containing Toll-like receptor (TLR) agonists. In this work, we hypothesized that using a micellar drug delivery platform, rather than a liposomal platform, could retain the benefits of nanoparticle delivery systems while avoiding PEG recognition and generation of anti-PEG antibodies. Indeed, micellar formulation of the TLR7 agonist 1V270 induced far lower anti-PEG antibody levels and was well tolerated while retaining a similar circulation profile across multiple dosing. Furthermore, 1V270-micelles showed strong efficacy as monotherapy in murine syngeneic cancer models and showed combinatorial efficacy with anti-PD1 treatment. Following intravenous administration, tumors developed an inflammatory reaction and macroscopic hemorrhage 6\u2009h post treatment followed by significant cell death 24\u2009h post treatment, which was not observed in spleens and livers. Tumors displayed strong innate signaling within 24\u2009h, which was accompanied by persistent massive infiltration of neutrophils and antigen-specific cytotoxic T cells, reduction in cancer cells and broad upregulation of immune-related genes. 1V270-micelles were well tolerated by non-human primates at doses equivalent to those displaying therapeutic activity in murine cancer models. Overall, the study provides novel insights into the mode of action of TLR7 agonists and demonstrates good and sustained tolerability of 1V270-micelles across animal models and excellent efficacy in murine cancer models by bridging innate and adaptive immunity.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf043","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T21:46:51Z","timestamp":1746049611000},"page":"1603-1616","source":"Crossref","is-referenced-by-count":2,"title":["Micellar formulation provides potent and tolerable TLR7 agonist treatment for anti-cancer immunotherapy"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5502-8372","authenticated-orcid":false,"given":"Esben","family":"Christensen","sequence":"first","affiliation":[{"name":"DTU Health Technology, Section for Cell and Drug Technologies, Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"MonTa Biosciences ApS , Kgs. Lyngby,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilla","family":"Stavnsbjerg","sequence":"additional","affiliation":[{"name":"DTU Health Technology, Section for Cell and Drug Technologies, Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Copenhagen University Hospital (Rigshospitalet) and University of Copenhagen , Copenhagen,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus","family":"M\u00fcnter","sequence":"additional","affiliation":[{"name":"DTU Health Technology, Section for Cell and Drug Technologies, Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bak","sequence":"additional","affiliation":[{"name":"DTU Health Technology, Section for Cell and Drug Technologies, Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. 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Lyngby,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten","family":"Petersen","sequence":"additional","affiliation":[{"name":"MonTa Biosciences ApS , Kgs. Lyngby,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Kempen","sequence":"additional","affiliation":[{"name":"DTU Health Technology, Section for Cell and Drug Technologies, Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"DTU Nanolab, National Centre for Nanofabrication and Characterization, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Jensen","sequence":"additional","affiliation":[{"name":"Hevesy Laboratory, Department of Health Technology, Technical University of Denmark , Roskilde,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-5547","authenticated-orcid":false,"given":"Andreas","family":"Kjaer","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Copenhagen University Hospital (Rigshospitalet) and University of Copenhagen , Copenhagen,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas R","family":"Henriksen","sequence":"additional","affiliation":[{"name":"DTU Health Technology, Section for Cell and Drug Technologies, Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders E","family":"Hansen","sequence":"additional","affiliation":[{"name":"DTU Health Technology, Section for Cell and Drug Technologies, Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]},{"name":"Center for Nanomedicine and Theranostics, Technical University of Denmark , Kgs. Lyngby,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Jensen","sequence":"additional","affiliation":[{"name":"MonTa Biosciences ApS , Kgs. 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