Benutzerspezifische Werkzeuge

Development and validation of tumor-selective bio-immunoconjugates in nanoparticle format for targeted cancer therapy (NANO:BICs)

European Social Fund (ESF) via Sächsische Aufbaubank (SAB)

New and innovative strategies of tumor therapy rely on the activation of the body’s own immune system to attack both the tumor as well as distant metastases. Intensive research is currently conducted on synthetic agonists targeting pattern recognition receptors (PRRs), which represent an important interface between innate immunity and adaptive immune system. As particularly promising synthetic agonists appear short single-stranded and double-stranded RNA molecules as well as CpG oligodeoxynucleotides (CpG-ODNs), which bind specifically to Toll-like receptors (TLR), a type of PRRs. Upon binding to the cognate ligands, TLRs mediate the initiation of antigen-specific adaptive immune response and release of proinflammatory cytokines. However, due to the negative net charge, TLR agonists cannot pass the cell membrane. Transport into the cell can be achieved by complexation with cationic carrier molecules. Nevertheless, the unspecific uptake of these complexes into normal cells or healthy tissues has a limiting effect.

The aim of the research project is the establishment and validation of functionalized bio-immunoconjugates (BICs) in nanoparticle format (NANO:BICs), which are specifically taken up into tumor cells via surface receptor-mediated endocytosis. For this purpose, the NANO:BICs are coupled with selected molecular targeting heads (tumor-specific antibodies and peptides) via an avidin-biotin interaction to selectively treat different tumor entities with synthetic TLR agonists independent of the patient's human leukocyte antigen (HLA) polymorphism. The selective transfer of TLR-agonist into tumor cells initiates production of inflammatory cytokines, especially type I interferons and induces their immunogenic cell death, thereby releasing tumor antigens. Our project aims to investigate to what extent the release of proinflammatory cytokines and tumor antigens reprograms the immunosuppressive tumor microenvironment and triggers an adaptive immune response to effectively eliminate the tumor cells.

The research project is supported by the Sächsische Aufbaubank (SAB) in cooperation with the Urological Research Laboratory and the Institute of Immunology of the Medical Faculty Carl Gustav Carus and the Leibniz Institute for Polymer Research in Dresden.

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