Abstract: The present invention presents an improved method for identification of neoepitopes useful in active immunotherapy targeting malignant neoplasms. The method integrates identification of somatic variants of expression product with a balanced evaluation of such variants' 1) ability to bind MHC, 2) ability to induce immune responses, 3) clonal coverage in the tumour tissue, and 4) ability to evade immune responses. Also, the method is complemented by a method for purposive deselection of neoepitopes that could induced undesired immune response against normal cells.

Abstract: A method for T-cell epitope prediction where quantitative scores of stability in the binding between peptides and MHC molecules are integrated into the derivation of the likelihood that a peptide of defined amino acid sequence constitutes a T-cell epitope. Preferably, stability data are obtained an MS-based method for identification of MHC binding peptides, where the binding capability is quantitatively assessed to allow distinction between stably binding peptides and peptides that are unlikely to be presented to T-cells. The method includes a step of time-course or thermostability testing of naturally processed peptides bound to MHC. Also disclosed are methods for preparation of personalized immunogenic compositions, methods of therapeutic treatment of malignancies, and a computer system that implements the T-cell epitope prediction method.