Revolutionary Platform to Decipher Immunogenicity of Tumour Neoantigens- the Ultimate Targets for Future Immunotherapies to Eradicate Cancer

Immunotherapy has revolutionised cancer treatment, providing survival benefits in patients with hard-to-treat tumours. Tragically, these benefits are unevenly distributed. Clinical efficacy varies dramatically between (and within) cancer types, and severe side-effects persist.

To address this, new treatment strategies seek the rational design of personalised therapies to achieve full eradication of most cancers.

Such a vision can be achieved by inducing immune responses against the ultimate tumour-specific targets: immunogenic tumour neoantigens (iNeoAg).

However, a major limitation is the lack of technologies to identify iNeoAg from the thousands of background mutations in tumours.

The DECOD-Ag consortium envisions a revolutionary technology realising an unbiased high-throughput transformative immunogenicity profiling platform that, for the first time, uniquely identifies iNeoAgs with the following enabling technologies: i) high throughput screening technology based on random mutagenesis and artificial antigen-presenting cells, to categorise immune recognition triplets (MHC-neoantigen-TCR), define the rules of neoantigen-T cell engagement and the immunogenicity of the neoantigen; ii) robust in silico prediction algorithms to predict neoantigen immunogenicity and neoantigen-T cell pairing; and iii) clinical validation workflow combining multiple advanced immune monitoring technologies.

The DECOD-Ag project will be conducted by world-leading, interdisciplinary scientists, with expertise in cancer immunotherapy, bioinformatics, peptidomics, mass spectrometry, immune monitoring, clinical and translational medicine.

The DECOD-Ag platform and GENESIS predictor will lead to a new frontier towards developing novel and effective anticancer therapies, with the radical potential to fully eradicate any tumour in any patient.