Scancell products

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 recognised 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, metastasis and immune evasion. Antibodies recognising tumour-associated glycans could therefore have excellent therapeutic potential.

During the development of the anti-glycan monoclonal antibodies (mAbs), Scancell identified unique sequence residues in the Fc region that enable mAbs to self-associate upon target recognition, resulting in more potent, high avidity antibodies.

ImmunoBody vaccines are designed to generate potent T cell responses capable of a broad anti-tumour effect. They are DNA vaccines that encode a protein in the form of an antibody, but the parts of the antibody that would normally bind to the target protein are replaced with epitopes from a cancer antigen.

Scancell’s lead ImmunoBody cancer vaccine, SCIB1, is being developed for the treatment of patients with metastatic melanoma. SCIB1 incorporates specific epitopes from the proteins gp100 and TRP-2, which were identified from the cloning of T cells from patients who achieved spontaneous recovery from melanoma skin cancers. Both proteins play key roles in the production of melanin in the skin.

The Modi-2 vaccine exploits a second post-translational modification, stimulating the production of CD4 T cells using tumour-associated peptide epitopes in which the lysine residues are converted to homocitrulline. This change occurs via a process known as carbamylation, leading to a change in molecular charge which, in turn, alters antigenic properties and can result in the generation of unique T cell epitopes.