An in situ depot for the sustained release of a TLR7/8 agonist in combination with a TGFβ inhibitor promotes anti-tumor immune responses
Year: 2024
Type: article
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, immunosuppressive 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 a sustained drug release depot at the injection site 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 to allow infiltration of T cells, consequently generating systemic anticancer immunoreactivity. The CarboCell technology can release multiple small molecule drugs - each with tailored release profiles - rendering it active across the broad composition of TME backgrounds. In the current study, impressive therapeutic performance is presented for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor. CarboCell can be injected through standard clinical thin-needle technologies. Its inherent magnetic resonance imaging and ultrasound visibility, and optional radiographic contrast, make it possible to validate and plan CarboCell injections across clinical imaging modalities. These features, in combination with attractive injection intervals, secure optimal patient compliance and open new possibilities for intratumoral immunotherapy accurately across basically all anatomical locations.
Source: Nature Communications
Authors: 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, Thomas L. Andresen
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
OpenAlex ID: W4402166497