Blocking the tumour-promoting effects of Fusobacterium nucleatum by eliciting an effective immune response against the tumour-binding Fap2 lectin

This Health Research BC and GlycoNet co-funded project focuses on Fusobacterium nucleatum (Fn), an oral gram-negative, anaerobic bacterium that can spread in the blood to colonize colorectal adenocarcinomas and other cancer types. Fn is found in ~50% of colorectal tumors and is associated with chemoresistance, metastasis, recurrence, and generally poor patient outcomes. Our overarching hypothesis is that immune interventions against Fn can mitigate its tumorpromoting effects. Tumour colonization by Fn is mediated by Fap2, a large (400 kDa) lectin that binds to host cell GalGalNAc, over-expressed by CRC tumour cells. Our objective for this project is to create recombinant, truncated forms of Fap2 with native conformation, which will serve as immunogens for the generation of candidate vaccines and mAbs that will then be tested in murine challenge models. In future work, we will aim to advance promising candidates to academic clinical trials.