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4 - In vivo Proof-of-Principle
This opportunity has produced a lead T-Cell Receptor mimic (TCRm) monoclonal antibody (mAb) against an HLA-A*0201 presented peptide derived from the cancer target p53, that is mutated in 50% of human tumours and deregulated in many more. Currently we have selectivity and specificity data on the lead mAb, with positive preliminary data for Antibody Dependent Cell-mediated Cytotoxicity (ADCC), Complement Dependent Cytotoxicity (CDC), Antibody Dependent Cellular Phagocytosis (ADCP), as well as in vivo efficacy data in a mouse xenograft model.
The lead anti-Jagged1 monoclonal antibodies (mAbs) come with a strong data package demonstrating high specificity and low nM affinity binding, as well as having been humanised and deimmunised by Lonza. There is clear in vitro inhibitory action against Jagged1 and its downstream targets. Efficacy has been demonstrated in vitro in 3D spheroids to a similar degree as the pan-Notch γ-secretase inhibitors and in vivo in breast cancer and ovarian cancer xenograft models. They bind to a novel Jagged1 epitope that distinguishes them from others in the field.
The integrin ɑvß6 is an exciting emerging target for both imaging and therapy across many common tumour types including pancreatic, breast, oesophagus, head and neck, skin, lung and ovarian. Each year an estimated 279,000 ɑvß6-positive tumours are diagnosed in the US & UK alone. In addition, ɑvß6 is recognised as an exciting target in fibriotic diseases.