Pre-clinical evaluation of immunoconjugates activating NK cells in cancer models

As a novel cancer immunotherapeutic approach, we generated two types of immunoconjugates, called CoMiX, that enhanced complement directed activity and cytotoxicity at the surface of HER2-tumour cells or CD20-overexpressing lymphomas. Based on the CoMix technology, we have generated recombinant molecules targeting and activating NK cells against different cell types infected with various pathogens. These molecules increase also the cytotoxic activity of NK cells against K562 and Raji cancer cells through IFN-y release and cytotoxic protein degranulation.
Pancreatic cancer is a cancer with highly unmet medical needs. Pancreatic cancer has a catastrophic prognosis (recent five year survival in the USA: 9.3%), and moreover is expected to become the second most frequent cancer in 2030. Treatment is difficult, as in most cases diagnosis is made at late stages when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients due to therapy resistance and a limited response to checkpoint inhibitors. Many pancreatic cancers are resistant to immunotherapeutic approaches due to their immune-hostile microenvironment
We propose here to evaluate novel immunoconjugates activating NK cell function against lymphoma and pancreatic cancer as compared to current therapies. The PhD student will develop different in vitro (2D and 3D cellular models) and in vivo (mouse models of lymphoma and pancreatic cancer) cancer models, evaluate several molecules activating NK cells against tumor cells, and investigate their mode of action using different immunoassays.