An in situ depot for the sustained release of a TLR7/8 agonist in combination with a TGFβ inhibitor

Sep 21, 2026

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An in situ intratumoral depot is presented to deliver a Toll-like receptor 7/8 agonist together with a transforming growth factor-β inhibitor directly within the tumor microenvironment. The strategy aims to overcome immunosuppressive barriers by creating a sustained, localized drug release source that trains and polarizes immune cells. The platform maintains an immune-activated state in tumor-draining lymph nodes and promotes systemic anticancer immunoreactivity, enabling hot-spot formation using standard thin-needle injection and imaging-visible positioning.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract and Background

CarboCell technology and rationale

Immunosuppressive tumor microenvironment and combination therapy

Intratumoral delivery challenges and controlled release solution

Preclinical Dual-Drug Strategy

Article [https://doi.org/10.1038/s41467-024-50967-w](https://doi.org/10.1038/s41467-024-50967-w) An in situ depot for the sustained release of a TLR7/8 agonist in combination with a TGFβ inhibitor promotes anti-tumor immune responses Received: 24 January 2023 | Accepted: 26 July 2024 | | --- | | | | Check for updates | Sophie B. Jensen 1, Ditte E. Jæhger1, Elizabeth Serrano-Chávez1, Hólmfríður R. Halldórsdóttir1, Trine B. Engel1, Jennifer S. Jørgensen1, Unnur J. Björgvinsdóttir1, Serhii Kostrikov 1, Marouschka J. Scheeper1, Lars Ringgaard1, Linda M. Bruun1, Camilla Stavnsbjerg1, Esben Christensen 1, Martin Bak1, Julianna Thuroczy 2, Lajos Balogh2, Andreas T. I. Jensen3, Fredrik Melander1, Andreas Kjaer 4,5, Jonas R. Henriksen1, Anders E. Hansen1 & Thomas L. Andresen 1 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 wereport 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. The anticancer immune response is generated in the antigen-rich cancerous tissue and in the associated lymph nodes1. In most cancer patients, the anticancer immune response is, however, counteracted by an immunosuppressive tumor microenvironment (TME), resulting in a poorly organized and uncoordinated adaptive immune response2,3. The immunosuppressive TME is a target that, if successfully transformed, can improve the outcome of cancer therapies4–6. Immune activating compounds, which activate and link the innate and 1Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. 2Animal Health Center Budafok, Budapest, Hungary. 3Department of Health Technology, Center for Nanomedicine and Theranostics, Technical University of Denmark, Roskilde, Denmark. 4Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Copenhagen, Denmark. 5Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. e-mail: [tlan@dtu.dk](tlan@dtu.dk) adaptive immune response, are among the most promising candidates to achieve this transformation7,8. However, systemic administration of these agents is challenging and has a signiﬁcant risk of dose-limiting toxicities at sub-therapeutic dose levels6,8–11. As explored previously, direct intratumoral drug administration of these agents offers a tolerated and therapeutically effective alternative that can further generate systemic anticancer immune responses10–14. Tumors are central sources of antigens expressed across multiple cancer cell clones; and, intratumoral therapies thus potentially stimulate a polyclonal in situ vaccination directly in the antigen-rich cancer tissue1. Therapeutic effects provided by free-drug injections are, however, often hampered by rapid loss of drug activity within the TME due to the lack of optima

FAQs

What is the main purpose of the in situ depot described in the article?

It provides sustained intratumoral release of immune-stimulatory drugs by forming a depot inside the tumor microenvironment, aiming to drive anti-tumor immune responses.

Which two drugs are delivered and what roles do they play?

A TLR7/8 agonist and a TGFβ inhibitor are co-delivered to link innate and adaptive immunity and to redirect immune cells toward anticancer phenotypes.

How does CarboCell support precise intratumoral administration?

It can be injected using standard thin-needle techniques and has inherent imaging contrast to help secure accurate intratumoral positioning.

Sep 21, 2026

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