RNA-based personalised breast cancer vaccines
Triple negative breast cancer (TNBC) is defined by the lack of oestrogen receptor (ER), progesterone receptor (PR) and the absence of HER-2 overexpression. TNBC is an aggressive cancer with a 5-year survival rate of less than 80 %. In addition, the molecular heterogeneity of TNBC frequently hampers the clinical benefit of common targeted therapies. Accumulating evidence indicates that TNBC tumours are highly immunogenic and possess tumour-specific antigens and tumour mutations. The EU-funded MERIT (Mutanome engineered RNA immuno-therapy) project aims to induce an integrated anti-tumour immune response directed against both shared and mutated tumour-antigens on an individual patient basis. For this purpose, the MERIT personalised treatment will utilise the huge potential of synthetic RNAs as vaccines. In this context, MERIT will combine two mRNA vaccine concepts. The WAREHOUSE vaccine concept ensures that each patient will receive a selection of RNAs from a pre-equipped RNA warehouse, which match the antigen-expression pattern of the patient's tumour. The MUTANOME vaccine concept is based on the identification of tumour-specific mutations by next generation sequencing and the on-demand manufacturing of RNAs that are derived from mutant epitopes. The RNAs will be administered intravenously as a nanoparticle formulation, delivered to antigen-presenting cells where they are expressed as proteins and presented to T cells. After setting up and optimising a clinical screening process for the presence of shared tumour antigens and mutations, the documents for the clinical trial application were prepared. The next step is to conduct a European multi-centre study to validate the clinical efficacy of this novel immunotherapeutic approach. MERIT is exploiting the large unique repertoire of antigenic targets of each patient instead of focusing on a small proportion of antigens shared by all patients. Completion of this trial envisages the clinical development of a new class of immunotherapies to solve current problems in anti-cancer drug development.
Keywords
RNA vaccines, breast cancer, tumour-specific antigens, mutations, mutanome, TNBC
