Neo-antigen Targeted Cancer Immunotherapy

Peptide-based cancer vaccines have failed in the past. Why is Targovax’s approach different?

Past efforts at developing cancer vaccines based on peptides have failed because of the length of peptides selected: peptides of short length were used that activated MHC class I dependent CD8+ cytotoxic T-cells only but, importantly, did not activate the critical MHC class II dependent CD4+ helper T-cells. This approach therefore took no account of the fact that both CD4+ and CD8+ T-cells are necessary to obtain a clinical efficient anti-cancer T-cell immune response.

Targovax has designed its neo-antigen immunotherapy with peptides that are sufficiently long as to be complexed with MHC class II molecules, and to allow antigen processing to shorter peptides that can be complexed with MHC class I molecules. Targovax’s targeted immunotherapies are therefore able to activate both mutant RAS specific CD8+ cytotoxic T-cells and CD4+ helper T-cells.

Peptides are not immunogenic by themselves. Peptides need an adjuvant that stimulates the immune system to recognize the peptides and to process them. The quality of the immune reaction to peptides is completely dependent on the adjuvant. In the past, some peptide cancer vaccines have failed because a wrong type of adjuvant was chosen. Targovax has selected the immune stimulator GM-CSF (granulocyte-macrophage colony-stimulating factor) as its adjuvant - one of the most potent adjuvants used for peptide vaccinations since the early 1980s, producing a very convincing track record of potency and effectiveness. Targovax avoids the side effects associated with systemic administration of GM-CSF by only injecting minute quantities intra-dermally. This is why Targovax believes it can succeed where previously others have failed - to the benefit of all patients with RAS mutated cancers.

Targovax’s RAS peptides and the adjuvant GM-CSF are inseparable components of the same product, as peptides alone are not immunogenic.

Berit Iversen
VP, Head of CMC

Peptides are small proteins. They can be produced chemically in quantities of many kilograms. RAS peptides are very stable and can be stored for several years.

T-cells are cells of the immune system that defend the host against intracellular changes and infections. By using peptides mimicking special intracellular changes, like RAS mutations, a subset of T-cells can be induced that recognizes cells with such mutations and triggers immunological eradication of these cells. T-cells also provide immunological memory and are rapidly retriggered upon reappearance of cells with the specific intracellular changes.

Read more about T-cells and the immune system.