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 ImmunBody® 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);
- Inclusion of motifs (e.g., GC rich regions) to ensure it is immunogenic and that it is taken up directly by dendritic cells;
- Retention of the Fc region of the protein form of 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 cytotoxic CD8 Tc cell responses and helper Th CD4 responses, which is important as Th cells are required for Tc activation and recruitment to the tumour site.
Scancell currently has two ImmunoBody® vaccines in development:
- SCIB1, a vaccine incorporating specific epitopes from two melanoma proteins (TRP-2 and gp100) and is designed to treat patients with skin cancer;
- SCIB2, a vaccine incorporating epitopes from the cancer testes antigen, NY-ESO-1, which is normally only expressed in germline cells, targets a variety of tumours, including non-small cell lung cancer.