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

Sophie B. Jensen, Ditte E. Jæhger, Elizabeth Serrano-Chávez, Hólmfríður R. Halldórsdóttir, Trine B. Engel, Jennifer S. Jørgensen, Unnur J. Björgvinsdóttir, Serhii Kostrikov, Marouschka J. Scheeper, Lars Ringgaard, Linda M. Bruun, Camilla Stavnsbjerg, Esben Christensen, Martin Bak, Julianna Thuroczy, Lajos Balogh, Andreas T. I. Jensen, Fredrik Melander, Andreas Kjaer, Jonas R. Henriksen, Anders E. Hansen and Thomas L. Andresen ()
Additional contact information
Sophie B. Jensen: Technical University of Denmark
Ditte E. Jæhger: Technical University of Denmark
Elizabeth Serrano-Chávez: Technical University of Denmark
Hólmfríður R. Halldórsdóttir: Technical University of Denmark
Trine B. Engel: Technical University of Denmark
Jennifer S. Jørgensen: Technical University of Denmark
Unnur J. Björgvinsdóttir: Technical University of Denmark
Serhii Kostrikov: Technical University of Denmark
Marouschka J. Scheeper: Technical University of Denmark
Lars Ringgaard: Technical University of Denmark
Linda M. Bruun: Technical University of Denmark
Camilla Stavnsbjerg: Technical University of Denmark
Esben Christensen: Technical University of Denmark
Martin Bak: Technical University of Denmark
Julianna Thuroczy: Animal Health Center Budafok
Lajos Balogh: Animal Health Center Budafok
Andreas T. I. Jensen: Technical University of Denmark
Fredrik Melander: Technical University of Denmark
Andreas Kjaer: Copenhagen University Hospital
Jonas R. Henriksen: Technical University of Denmark
Anders E. Hansen: Technical University of Denmark
Thomas L. Andresen: Technical University of Denmark

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract 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-β inhibitor in preclinical tumor models in female mice.

Date: 2024
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DOI: 10.1038/s41467-024-50967-w

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