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.
The key design features of an ImmunoBody® vaccine include:
- Epitopes that bind to both MHC class I (for the cytotoxic CD8 Tc cell response) and MHC class II (for the helper CD4 Th cell response).
- Retention of the Fc region of the protein forms the ImmunoBody® which targets activated dendritic cells via its specific receptor.
The most important aspect of the ImmunoBody® technology is the ability to initiate both direct and cross-presentation of epitopes to T cells. There are various pathways by which dendritic cells can process antigen, but the highest avidity T cell responses (i.e., the most potent) are generated if more than one pathway is used to present the same epitope. In the case of ImmunoBody®, the DNA form is taken up and processed directly by dendritic cells whereas the protein form (which is produced from the DNA in cells at the site of the injection) binds to the high affinity Fc receptor on dendritic cells leading to cross-presentation. As a result of both the direct and cross-presentation, the T cells not only have a higher avidity (up to 100-fold increased potency), but there are many more T cells generated against the epitopes of interest.
Immunisation with ImmunoBody® vaccines generates both CD8 cytotoxic T lymphocyte (CTL) responses and helper Th CD4 responses, which is important as Th cells are required for CTL activation and recruitment to the tumour site.
Scancell’s lead ImmunoBody® vaccine is SCIB1, a vaccine incorporating specific epitopes from two melanoma proteins (TRP-2 and gp100). SCIB1 is designed to treat patients with skin cancer and is currently in Phase 2 development in combination with the checkpoint inhibitor, Keytruda®.
SCIB2 is a vaccine incorporating epitopes from the cancer antigen, NY-ESO-1, and targets a variety of tumours, including non-small cell lung cancer.
The utility of the ImmunoBody® platform has recently been expanded by the application of AvidiMab®, which has increased the potency of these vaccines whilst also extending the patent lifetime of the ImmunoBody® platform. The iSCIB1+ vaccine is an AvidiMab® modified version of SCIB1 which includes additional epitopes so it can be used to treat all melanoma patients irrespective of their human leukocyte antigen (HLA) tissue type. The iSCIB2 vaccine is an AvidiMab® modified version of SCIB2. Preclinical data shows both iSCIB1+ and iSCIB2 have excellent anti-tumour efficacy.
The COVIDITY programme is also based on Scancell ImmunoBody® technology and is aimed at developing a next-generation DNA-based COVID-19 vaccine to be administered using needle-free injection systems.