ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer. Academic Article uri icon

Overview

abstract

  • Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is treated with ALK tyrosine kinase inhibitors (TKIs), but the lack of activity of immune checkpoint inhibitors (ICIs) is poorly understood. Here, we identified immunogenic ALK peptides to show that ICIs induced rejection of ALK+ tumors in the flank but not in the lung. A single-peptide vaccination restored priming of ALK-specific CD8+ T cells, eradicated lung tumors in combination with ALK TKIs and prevented metastatic dissemination of tumors to the brain. The poor response of ALK+ NSCLC to ICIs was due to ineffective CD8+ T cell priming against ALK antigens and is circumvented through specific vaccination. Finally, we identified human ALK peptides displayed by HLA-A*02:01 and HLA-B*07:02 molecules. These peptides were immunogenic in HLA-transgenic mice and were recognized by CD8+ T cells from individuals with NSCLC, paving the way for the development of a clinical vaccine to treat ALK+ NSCLC.

authors

  • Mota, Inês
  • Patrucco, Enrico
  • Mastini, Cristina
  • Mahadevan, Navin R
  • Thai, Tran C
  • Bergaggio, Elisa
  • Cheong, Taek-Chin
  • Leonardi, Giulia
  • Karaca-Atabay, Elif
  • Campisi, Marco
  • Poggio, Teresa
  • Menotti, Matteo
  • Ambrogio, Chiara
  • Longo, Dario L
  • Klaeger, Susan
  • Keshishian, Hasmik
  • Sztupinszki, Zsófia M
  • Szallasi, Zoltan
  • Keskin, Derin B
  • Duke-Cohan, Jonathan S
  • Reinhold, Bruce
  • Carr, Steven A
  • Wu, Catherine J
  • Moynihan, Kelly D
  • Irvine, Darrell J
  • Barbie, David A
  • Reinherz, Ellis L
  • Voena, Claudia
  • Awad, Mark M
  • Blasco, Rafael B
  • Chiarle, Roberto

publication date

  • July 10, 2023

Identity

Scopus Document Identifier

  • 78049489760

Digital Object Identifier (DOI)

  • 10.1021/ac102387t

PubMed ID

  • 37430060

Additional Document Info