Unraveling the power of NAP-CNB's machine learning-enhanced tumor neoantigen prediction.

Journal: eLife
PMID:

Abstract

In this study, we present a proof-of-concept classical vaccination experiment that validates the in silico identification of tumor neoantigens (TNAs) using a machine learning-based platform called NAP-CNB. Unlike other TNA predictors, NAP-CNB leverages RNA-seq data to consider the relative expression of neoantigens in tumors. Our experiments show the efficacy of NAP-CNB. Predicted TNAs elicited potent antitumor responses in mice following classical vaccination protocols. Notably, optimal antitumor activity was observed when targeting the antigen with higher expression in the tumor, which was not the most immunogenic. Additionally, the vaccination combining different neoantigens resulted in vastly improved responses compared to each one individually, showing the worth of multiantigen-based approaches. These findings validate NAP-CNB as an innovative TNA identification platform and make a substantial contribution to advancing the next generation of personalized immunotherapies.

Authors

  • Almudena Mendez-Perez
    Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • Andres M Acosta-Moreno
    Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • Carlos Wert-Carvajal
    Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • Pilar Ballesteros-Cuartero
    Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • Ruben Sanchez-Garcia
    GN7 of the Spanish National Institute for Bioinformatics (INB), Biocomputing Unit, National Center of Biotechnology (CSIC), Instruct Image Processing Center, Madrid, Spain.
  • Jose R Macias
    Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • Rebeca Sanz-Pamplona
    Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Ramon Alemany
    Procure Program, Institut Català d'Oncologia-Oncobell Program, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Carlos Oscar Sorzano
    Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • Arrate Muñoz-Barrutia
    Bioengineering and Aerospace Engineering Department, Universidad Carlos III de Madrid and Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. mamunozb@ing.uc3m.es.
  • Esteban Veiga
    Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.