Colorectal carcinoma (CRC) is the second and third most common cause of cancer death in women and men, respectively, causing a significant burden on the European patient population.1 CRC can be broadly subdivided into adenocarcinoma-type CRC (aCRC) and mucinous-type CRC (mucinous CRC), which can both be characterised by an overproduction of mucins. The natural functions of mucins can be exploited by tumour cells to form a 'barrier' that impedes the accessibility of current CRC therapies to their target receptors. Thus, mucins contribute to the development of drug resistance and can drive carcinogenesis. Specifically, mucins impede antibody-mediated cancer therapies such as cetuximab and trastuzumab that target the epithelial growth factor receptor (EGFR) and HER2 receptor.4,5 Mucins, therefore, are an unaddressed (and literal) physical obstacle in the fight against CRC (and other cancers with high mucin expression) that hinders the anti-cancer activity of otherwise promising drugs. In the Strijbis group, we applied a bacterial mucinase enzyme called StcE to remove mucin proteins from the tumor surface and improve targeting of CRC drugs to surface receptors. With MUC-BITE, we aim to develop a mucinase-nanobody biological for the targeted delivery of StcE mucinase to tumour tissue to cleave tumorigenic mucins enhancing CRC therapies.
During this PoC project, we will determine the technical and commercial feasibility Nano-MUCase through the following activities:
1. Validate the capabilities of the Nano-MUCase to target CRC tumours and reduce mucin interference of anti-CRC drugs in organoid samples and in vivo.
2. Define an IP strategy by performing a thorough IP landscape and patentability analysis.
3. Conduct market research to discover potential customers/industrial partners, analyse competitors and identify a feasible roadmap to commercialisation.
4. Formulate a detailed business case to guide the commercialisation of the Nano-MUCase to penetrate the market and deliver a new therapeutic strategy to benefit CRC patients.
