Non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase inhibitors (TKI), but the treatment is successful for only a limited amount of time; most patients experience a relapse due to the development of drug resistance. Here, we show that a vaccine against ALK induced a strong and specific immune response that both prophylactically and therapeutically impaired the growth of ALK-positive lung tumors in mouse models. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. We found that lung tumors containing ALK rearrangements induced an immunosuppressive microenvironment, regulating the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti-PD-1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune checkpoint blockade therapies might represent a powerful strategy for the treatment of ALK-driven NSCLC. Cancer Immunol Res; 1-11. ©2015 AACR.

Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors

VOENA, claudia
First
;
MENOTTI, MATTEO;MASTINI, CRISTINA;DI GIACOMO, FILOMENA;LONGO, DARIO LIVIO;CASTELLA, BARBARA;AMBROGIO, CHIARA;MINERO, Valerio Giacomo;POGGIO, TERESA;MARTINENGO, CINZIA;D'AMICO, LUCIA;PANIZZA, ELENA;CAVALLO, Federica;ALTRUDA, Fiorella;INGHIRAMI, Giorgio;CHIARLE, Roberto
Last
2015-01-01

Abstract

Non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase inhibitors (TKI), but the treatment is successful for only a limited amount of time; most patients experience a relapse due to the development of drug resistance. Here, we show that a vaccine against ALK induced a strong and specific immune response that both prophylactically and therapeutically impaired the growth of ALK-positive lung tumors in mouse models. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. We found that lung tumors containing ALK rearrangements induced an immunosuppressive microenvironment, regulating the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti-PD-1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune checkpoint blockade therapies might represent a powerful strategy for the treatment of ALK-driven NSCLC. Cancer Immunol Res; 1-11. ©2015 AACR.
2015
100
112
ALK-DNA vaccine, ALK-rearranged NSCLC, PD-L1, lung cancer immunotherapy
Voena, Claudia; Menotti, Matteo; Mastini, Cristina; Di Giacomo, Filomena; Longo, Dario Livio; Castella, Barbara; Merlo, Maria Elena Boggio; Ambrogio, Chiara; Wang, Qi; Minero, Valerio Giacomo; Poggio, Teresa; Martinengo, Cinzia; D'Amico, Lucia; Panizza, Elena; Mologni, Luca; Cavallo, Federica; Altruda, Fiorella; Butaney, Mohit; Capelletti, Marzia; Inghirami, Giorgio; Jänne, Pasi A; Chiarle, Roberto
File in questo prodotto:
File Dimensione Formato  
Voena et al..pdf

Open Access dal 30/09/2016

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 2.37 MB
Formato Adobe PDF
2.37 MB Adobe PDF Visualizza/Apri
pubb6.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 2.14 MB
Formato Adobe PDF
2.14 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1530589
Citazioni
  • ???jsp.display-item.citation.pmc??? 27
  • Scopus 41
  • ???jsp.display-item.citation.isi??? 39
social impact