A key challenge in developing therapeutic vaccines against cancer is getting the correct vaccine target delivered to the correct immune cells in the correct cellular context. A variety of mRNA-based approaches are showing great promise in achieving these goals. mRNA vaccines can be integrated into flexible and modular immunotherapeutic strategies designed to address the specific needs of persons with cancer. Flexible approaches make mRNA vaccines ideal for the development of personalised precision approaches to drive immune responses to neoantigens from the patient’s own tumour.

Every form of cancer originates from a healthy cell. The developing immune system is educated to tolerate protein antigens expressed by healthy cells as “self” antigens. Cancer occurs when healthy cells start to break free from multiple layers of genetic mechanisms that restrict and suppress cellular replication, leading to uncontrolled and inappropriate proliferation. As a tumour develops, the malignant cells often begin to express proteins that serve as potential anti-tumour immune targets, or Tumour Associated Antigens (TAAs). 

As part of this process, malignant cells generally lose the quality control mechanisms that ensure high-fidelity DNA replication, such that growing tumours can express increasing quantities of proteins representing genetic mutations. These mutations often encode peptide sequences or “neoantigens” that are different enough from the self-sequence that the immune system may recognise them as “non-self.” Aside from neoantigens, TAAs may include unmutated self-proteins expressed in an inappropriate context.