ALK Peptide Vaccination Restores the Immunogenicity of ALK-rearranged Non-small Cell Lung Cancer

Overview

Journal Nat Cancer

Specialty Oncology

Date 2023 Jul 10

PMID 37430060

Authors

Ines Mota

Enrico Patrucco

Cristina Mastini

Navin R Mahadevan

Tran C Thai

Elisa Bergaggio

Taek-Chin Cheong

Giulia Leonardi

Elif Karaca-Atabay

Marco Campisi

Teresa Poggio

Matteo Menotti

Chiara Ambrogio

Dario L Longo

Susan Klaeger

Hasmik Keshishian

Zsofia M Sztupinszki

Zoltan Szallasi

Derin B Keskin

Jonathan S Duke-Cohan

Bruce Reinhold

Steven A Carr

Catherine J Wu

Kelly D Moynihan

Darrell J Irvine

David A Barbie

Ellis L Reinherz

Claudia Voena

Mark M Awad

Rafael B Blasco

Roberto Chiarle

Affiliations

Soon will be listed here.

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.

Citing Articles

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