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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.

SCIB2 is the second cancer vaccine based on the ImmunoBody® technology and encodes a modified antibody engineered to express the cancer antigen NY-ESO-1. This is a well-characterised and validated cancer target, being overexpressed in several tumour types including synovial sarcomas, oesophageal, liver, gastric, prostate and lung cancers.

Modi-1 is the first vaccine based on Scancell’s Moditope® platform. The vaccine is composed of a combination of three peptides from two target antigens that are commonly modified in cancer cells. The first is the cytoskeletal protein, vimentin, which is preferentially digested during autophagy. All mesenchymal tumours such as endometrial, renal, sarcomas, lymphomas and lung tumours express vimentin as their major cytoskeletal protein and are potential targets for a modified vimentin vaccine. In addition, many epithelial tumours, such as breast, ovarian, gastrointestinal and prostate switch from expression of cytokeratin to vimentin during metastasis in a process known as epithelial mesenchymal transition (EMT). This change in phenotype enables the cell to become mobile and metastasize to new locations in the body.

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.

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.