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VENUS, a Novel Selection Approach to Improve the Accuracy of Neoantigens’ Prediction

Authors :
Guido Leoni
Anna Morena D’Alise
Fabio Giovanni Tucci
Elisa Micarelli
Irene Garzia
Maria De Lucia
Francesca Langone
Linda Nocchi
Gabriella Cotugno
Rosa Bartolomeo
Giuseppina Romano
Simona Allocca
Fulvia Troise
Alfredo Nicosia
Armin Lahm
Elisa Scarselli
Source :
Vaccines, Vol 9, Iss 8, p 880 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Neoantigens are tumor-specific antigens able to induce T-cell responses, generated by mutations in protein-coding regions of expressed genes. Previous studies demonstrated that only a limited subset of mutations generates neoantigens in microsatellite stable tumors. We developed a method, called VENUS (Vaccine-Encoded Neoantigens Unrestricted Selection), to prioritize mutated peptides with high potential to be neoantigens. Our method assigns to each mutation a weighted score that combines the mutation allelic frequency, the abundance of the transcript coding for the mutation, and the likelihood to bind the patient’s class-I major histocompatibility complex alleles. By ranking mutated peptides encoded by mutations detected in nine cancer patients, VENUS was able to select in the top 60 ranked peptides, the 95% of neoantigens experimentally validated including both CD8 and CD4 T cell specificities. VENUS was evaluated in a murine model in the context of vaccination with an adeno vector encoding the top ranked mutations prioritized in the MC38 cell line. Efficacy studies demonstrated anti tumoral activity of the vaccine when used in combination with checkpoint inhibitors. The results obtained highlight the importance of a combined scoring system taking into account multiple features of each tumor mutation to improve the accuracy of neoantigen prediction.

Details

Language :
English
ISSN :
2076393X
Volume :
9
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Vaccines
Publication Type :
Academic Journal
Accession number :
edsdoj.70ac80030d6e4d77a7634edce691717b
Document Type :
article
Full Text :
https://doi.org/10.3390/vaccines9080880