FIELD: molecular biology.
SUBSTANCE: method for selecting tumor neoantigens for use in a personalized vaccine is described. Neoantigens are determined in a sample of cancer cells taken from an individual, wherein each neoantigen is contained in a coding sequence, contains at least one mutation in the coding sequence resulting in a change in the encoded amino acid sequence that is not present in a sample of non-cancerous cells of the specified individual, and consists of 9 to 40 contiguous amino acids of the coding sequence in a sample of cancer cells. For each neoantigen, the frequencies of mutant alleles of each of the specified mutations in the coding sequence are determined. The expression level of each coding sequence is determined in a sample of cancer cells or based on a cancer expression database of the same type as the sample of cancer cells. The binding affinity of the neoantigens to MHC class I is predicted. The neoantigens are ranked according to the values previously determined for each neoantigen, from the largest to the smallest value, providing the first, second and third list of ranks. The rank sum is calculated based on the first, second and third list of ranks and the distribution of neoantigens based on increase of the rank sum to obtain a ranked list of neoantigens, wherein the rank sum is a weighted rank sum, where the number of neoantigens is added to the rank value of each neoantigen. 30-240 neoantigens are selected from a ranked list of neoantigens, starting with the lowest rank. A method for constructing a personalized vector encoding a list of neoantigens selected by the method for use in form of a vaccine is also described. An expression vector encoding a list of neoantigens is presented. A collection of expression vectors is presented, each of which encodes part of the list of neoantigens.
EFFECT: claimed invention expands the arsenal of drugs for treating cancer.
15 cl, 8 dwg, 9 tbl, 4 ex
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Authors
Dates
2023-12-13—Published
2019-11-15—Filed