Jensen et al. demonstrated the potential of CarboCell technology – an adjustable and trackable drug-release depot that is injected as a liquid, but transforms into a semisolid scaffold – by evaluating the intratumoral delivery of a TLR7/8 agonist alone or in combination with a TGFβ inhibitor. In various tumor models, CarboCell co-delivery of these synergistic drugs enhanced T cell activation and infiltration, reprogrammed Tregs, induced tumor regression (including abscopal and anti-metastatic effects), protected mice from rechallenge, and synergized with checkpoint blockades. CarboCell was also well confined and well tolerated in canines.
Contributed by Lauren Hitchings
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-_ inhibitor in preclinical tumor models in female mice.
Author Info: (1) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (2) Department of Health Technology, Biot
Author Info: (1) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (2) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (3) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (4) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (5) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (6) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (7) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (8) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (9) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (10) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (11) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (12) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (13) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (14) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (15) Animal Health Center Budafok, Budapest, Hungary. (16) Animal Health Center Budafok, Budapest, Hungary. (17) Department of Health Technology, Center for Nanomedicine and Theranostics, Technical University of Denmark, Roskilde, Denmark. (18) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (19) Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Copenhagen, Denmark. Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. (20) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (21) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. (22) Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kgs. Lyngby, Denmark. tlan@dtu.dk.
