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. J?hger
;
Elizabeth Serrano-Chávez
, et al.
Nat. Commun.,2024,15,7687.
DOI:
10.1038/s41467-024-50967-w
PubMed ID:
39227589
More
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, fun_x005f_x0002_damental 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, conse_x005f_x0002_quently 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 sus_x005f_x0002_tained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor in preclinical tumor models in female mice.
Purchased from AmBeed:
144875-48-9
CarboCell combinatorial immunotherapy orchestrates curative anticancer immune activation of the tumor microenvironment
Sophie Jensen
;
Elizabeth Serrano-Chávez
;
Hólmfridur Halldórsdóttir
, et al.
Technical University of Denmark,2023.
DOI:
10.21203/rs.3.rs-2511064/v1
More
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.
Purchased from AmBeed:
144875-48-9
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
