Final Report Summary - MERIT (Mutanome Engineered RNA Immuno-Therapy)
The Mutanome Engineered RNA Immuno-Therapy (MERIT) project was funded by the European Commission under the 7th Framework Programme and ran from 2013 to 2017. A pioneering ribonucleic acid (RNA)-based immunotherapy approach to target individual tumor antigen signatures and create a biomarker-guided personalized treatment of cancer should be clinically translated and industrially validated. MERIT was implemented by a consortium of five European partners in academia and industry. The scientific-technological work program was structured into seven work packages (WPs), covering preclinical, clinical, project management, and dissemination activities.
A novel, highly personalized and on-demand manufactured RNA vaccine-based immunotherapy for patients with triple-negative breast cancer (TNBC) was investigated. The vaccine was tailored to the individual genomic profile of the tumour of each patient. The main objective of the project was to assess the clinical safety, feasibility and biological efficacy of the MERIT approach in a multi-center phase I/II trial. Until the end of the MERIT project funding, ten patients were vaccinated with RNA Warehouse vaccines coding for shared tumor-associated antigens (TAAs) The treatments were well-tolerated and a primary immune response analysis indicated that immune system activation was triggered by the RNA Warehouse vaccinations. The TNBC-MERIT trial will be continued after the funding period and the first vaccination with the highly individualized Mutanome RNAs, targeting patient-individual mutations, is planned for Q1 2018.
The project also included a broad scientific program: (i) The Development of a fast and accurate mutation caller (ConfIdent) as well as a fast and reliable sequencing read aligner (ComPass) have been finalized and a new pattern recognition semi-metric, Poisson-Binomial Radius (PBR) for mutational analysis was implemented. (ii) T-cell priming experiments providing evidence for development of T-cell memory upon RNA(LIP) immunization (iii) the capacity of Protamine-RNA nanoparticles (“PR particles”) of different sizes and surface charges to induce steerable immunomodulation were evaluated in mice and (iv) the optimal combination therapy for treatment of metastasized disease as well as several packaging systems to enhance the uptake and cell tropism of the injected mRNA have been determined.
The MERIT concept and clinical trial design have been presented to a broad audience on numerous conferences. Scientific publications compiling data of the MERIT project are planned after completion of the clinical trial. Please visit the project webpage at http://merit-consortium.eu/ for further information.
A novel, highly personalized and on-demand manufactured RNA vaccine-based immunotherapy for patients with triple-negative breast cancer (TNBC) was investigated. The vaccine was tailored to the individual genomic profile of the tumour of each patient. The main objective of the project was to assess the clinical safety, feasibility and biological efficacy of the MERIT approach in a multi-center phase I/II trial. Until the end of the MERIT project funding, ten patients were vaccinated with RNA Warehouse vaccines coding for shared tumor-associated antigens (TAAs) The treatments were well-tolerated and a primary immune response analysis indicated that immune system activation was triggered by the RNA Warehouse vaccinations. The TNBC-MERIT trial will be continued after the funding period and the first vaccination with the highly individualized Mutanome RNAs, targeting patient-individual mutations, is planned for Q1 2018.
The project also included a broad scientific program: (i) The Development of a fast and accurate mutation caller (ConfIdent) as well as a fast and reliable sequencing read aligner (ComPass) have been finalized and a new pattern recognition semi-metric, Poisson-Binomial Radius (PBR) for mutational analysis was implemented. (ii) T-cell priming experiments providing evidence for development of T-cell memory upon RNA(LIP) immunization (iii) the capacity of Protamine-RNA nanoparticles (“PR particles”) of different sizes and surface charges to induce steerable immunomodulation were evaluated in mice and (iv) the optimal combination therapy for treatment of metastasized disease as well as several packaging systems to enhance the uptake and cell tropism of the injected mRNA have been determined.
The MERIT concept and clinical trial design have been presented to a broad audience on numerous conferences. Scientific publications compiling data of the MERIT project are planned after completion of the clinical trial. Please visit the project webpage at http://merit-consortium.eu/ for further information.
