Project

starter scholarship EVDS Ruben De Coen: OncoRham

Code
365J01217
Duration
01 October 2017 → 30 September 2018
Funding
Funding by bilateral agreement (private and foundations)
Research disciplines
  • Medical and health sciences
    • Biomarker discovery and evaluation
    • Drug discovery and development
    • Medicinal products
    • Pharmaceutics
    • Pharmacognosy and phytochemistry
    • Pharmacology
    • Pharmacotherapy
    • Toxicology and toxinology
    • Other pharmaceutical sciences
 
Project description

Cancer remains a leading cause of death and traditional treatment options for cancer patients include surgicalresection, direct irradiation and cytotoxic chemotherapy, all of which are prone to causing severe side effects. Recently, immune-engineering, has emerged as an exciting new field of research. Currently, the field is dominated by monoclonal antibodies or cell-based therapeutics which involve an extreme cost of development and production and only have a very limited shelf life, all of which poses a huge burden on society and health care agencies. Therefore, therapeutic strategies based on simpler synthetic compounds that can recruit endogenous antibodies (i.e. antibodies present in large amounts in every individual) towards the tumour site to exert ·subsequent antibody-mediated cell killing effects might be of great relevance. In my PhD project, I am developing synthetic polymers that recruit endogenous antibodies (i.e. antibodies present in the bloodstream of every individual) to solid tumours to exert subsequent cancer cell killing effects. To this end I have developed synthetic polymers that are composed of a cholesteryl amine motif that efficiently inserts into the membrane of target cells and promotes cell surface recycling from endosomal compartments after endocytosis. The backbone of the polymer is composed of rhamnose repeating units. About 2-3% of all lgG in human serum is directed against rhamnose owing to our gut microbiome. These high levels of anti-rhamnose antibodies are attractive for recruitment to target cells for triggering a series of complement- and antibody-mediated innate immune mechanisms. So far, I have proven in the lab that opposed to small antibody-recruiting molecules that contain only one rhamnose motif, polymer constructs instigate a dramatic increase in the recruitment of endogenous antibodies to the target cell surface. Currently, we are evaluating the in vftro cytotoxic effect of tethering these polymers to the cancer cell surface. I am applying for a EvdS scholarship to evaluate the therapeutic potential of our approach in in vivo tumour mouse models.