Proteogenomics Platforms Establishing Personalized and Precision Neoantigen Therapeutics in Cancer

The project aims to establish proteogenomics platforms to discover new sources of cancer neoantigens.
One of the study models will be T-cell lymphoma which is considered of high unmet clinical need and
which is of high priority focus in developed countries. Comparing the proteogenomic data of cancer
and normal samples will produce a rich source of mutant antigenic material, since several recurrent
genetic abnormalities have been discovered in such lymphomas.
The first stage of the project will be to use current bioinformatics software to define mutated genes,
mutant mRNA, RNA editing events, intron-translation, and chromosomal fusions from next
generation DNA and RNA sequencing to create a mutant protein reference database that is patient
specific; and this reference database would be a tool for identifying mutated MHC class I peptides
using mass spectrometry.
Next step will include
developing cell and tissue models to measure the dominating neoantigen
source in human cancers. Mass spectrometric assays will measure the extent to which all sources of
neopeptides are derived from tumour cells.
Last stage of the project will focus on developing vaccine models. Applying the above platform to in
vitro models, gives the basis to identification of cytotoxic T-cell clones from patients and testing for
T-cell killing of the lymphoma populations in vitro in combination with sets of mutant peptide
vaccines.
The key question would be whether inhibition of RNA splicing, or non-sense RNA decay increases
MHC Class I -mutated antigen presentation but also sensitize to existing T-cells isolated from
patients.