Glycosylation is a post-translational modification that occurs inside the cell and results in the addition of sugar motifs, “glycans”, to proteins and lipids that are, in most cases, destined for the cell surface. These glycan structures form the “glycome” and play an integral role in cell-to-cell and cell-to-matrix interactions through modulation of adhesion and cell trafficking. Glycosylation is increasingly recognized as a modulator of the malignant phenotype of cancer cells, where the interaction between cells and the tumour micro-environment is altered to facilitate processes such as drug resistance and metastasis. Antibodies recognising tumour-associated glycans could therefore have strong therapeutic potential. The challenge has been to produce high affinity monoclonal antibodies (mAbs) recognising these small sugars. Scancell has overcome this limitation and produced a series of high affinity mAbs targeting glycans that are highly over-expressed on cancer cells, and which directly lyse tumour cells without the need for the complement system or immune effector cells. This is a form of immunogenic cell death (ICD) and has the potential to initiate an anti-tumour immune response following the secretion of damage-associated molecular patterns (DAMPs), leading to long-term tumour control. Additionally, as the same glycans can be expressed by a wide range of proteins and lipids, the mAbs can be simultaneously used for drug delivery (antibody drug conjugates: ADC), as chimeric antigen receptor T cells (CAR-T) or for redirected T cell killing. The mAbs could therefore be a combination therapy in their own right.
When Scancell’s anti-glycan mouse mAbs were humanised for clinical use they lost their ability to kill tumour cells directly. Scancell has now patent protected a technology platform (AvidiMab™) which increases the avidity of human antibodies by promoting non-covalent Fc-Fc interactions. This modification reinstates the direct tumour cell killing ability of the anti-glycan humanised mAbs but could also be used to increase the potency of any human mAb and is available for licensing.