Software for profiling tumor neoantigens for the development of patient specific cancer therapies

Offentlig prosjektsammendrag

While scientists have struggled for over a century to harness the power of the immune system in the fight against cancer, it is only recently that the field has come of age. Immunotherapy drugs such as ipilimumab and pembrolizumab have been shown to be effective across multiple cancer indications including melanoma, lung cancer and colorectal cancer. These drugs work by taking the brakes off a patient's immune system and enabling it to mount a response against mutated proteins on the tumor's surface known as "neoantigens". However, despite the success of these new immunotherapies, they only work in a subset of patients. Thus, there is a desperate need for tools that stratify patients, and to develop more personalized approaches that can directly induce immune responses against selected neoantigen targets, through vaccination or the administration of genetically engineered T-cells. To achieve this ambitious goal OncoImmunity has developed machine learning-based software called the Immune Profiler which can identify optimal neoantigen targets from next generation sequencing (NGS) data - a method for profiling the mutational landscape of a tumor. However, the current software only identifies conventional neoantigens that induce the cellular arm of the immune system. The goal of this project is to work with our national and international collaborators to clinically validate the current Immune Profiler software and to extend the predictive capabilities of the software to cover non-conventional neoantigens. These include neoantigens created by post translational modifications (such as phosphorylation) or non-HLA restricted neoantigens that stimulate antibody responses. The outcome will be a tool that can generate a more holistic immune-system-orientated overview of a tumor's neoantigen landscape, which will improve patient stratification, patient monitoring and also broaden the repertoire of targets that can be engineered into personalized cancer vaccines and CAR-T-cells.