An in situ depot for the sustained release of a TLR7/8 agonist in combination with a TGFβ inhibitor promotes anti-tumor immune responses

被引：1

作者：

Jensen, Sophie B. ^{[1
]}

Jaehger, Ditte E. ^{[1
]}

Serrano-Chavez, Elizabeth ^{[1
]}

Halldorsdottir, Holmfriur R. ^{[1
]}

Engel, Trine B. ^{[1
]}

Jorgensen, Jennifer S. ^{[1
]}

Bjoergvinsdottir, Unnur J. ^{[1
]}

Kostrikov, Serhii ^{[1
]}

Scheeper, Marouschka J. ^{[1
]}

Ringgaard, Lars ^{[1
]}

Bruun, Linda M. ^{[1
]}

Stavnsbjerg, Camilla ^{[1
]}

Christensen, Esben ^{[1
]}

Bak, Martin ^{[1
]}

Thuroczy, Julianna ^{[2
]}

Balogh, Lajos ^{[2
]}

Jensen, Andreas T. I. ^{[3
]}

Melander, Fredrik ^{[1
]}

Kjaer, Andreas ^{[4
,5
]}

Henriksen, Jonas R. ^{[1
]}

Hansen, Anders E. ^{[1
]}

Andresen, Thomas L. ^{[1
]}

机构：

[1] Tech Univ Denmark, Dept Hlth Technol, Biotherapeut Engn & Drug Targeting, Lyngby, Denmark

[2] Anim Hlth Ctr Budafok, Budapest, Hungary

[3] Tech Univ Denmark, Dept Hlth Technol, Ctr Nanomed & Theranost, Roskilde, Denmark

[4] Copenhagen Univ Hosp, Dept Clin Physiol & Nucl Med, Copenhagen, Denmark

[5] Univ Copenhagen, Dept Biomed Sci, Cluster Mol Imaging, Copenhagen, Denmark

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

INTRATUMORAL IMMUNOTHERAPY; TUMOR; MICROENVIRONMENT; METASTASES; PATHWAY; BIOPSY;

D O I：

10.1038/s41467-024-50967-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic TME, and the poor systemic tolerability of immune activating drugs are, however, fundamental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming an intratumoral sustained drug release depot that provides high payloads of immune stimulatory drugs selectively within the TME. The CarboCell thereby induces a hot spot for immune cell training and polarization and further drives and maintains the tumor-draining lymph nodes in an anticancer and immune activated state. Mechanistically, this transforms cancerous tissues, consequently generating systemic anticancer immunoreactivity. CarboCell can be injected through standard thin-needle technologies and has inherent imaging contrast which secure accurate intratumoral positioning. In particular, here we report the therapeutic performance for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-beta inhibitor in preclinical tumor models in female mice.

引用

页数：18