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Cancer Immunol Res. 2015 Dec;3(12):1333-1343. doi: 10.1158/2326-6066.CIR-15-0089. Epub 2015 Sep 29.

Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors.

Author information

1
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
2
Center for Experimental Research and Medical Studies (CERMS), Città della Salute e della Scienza, Torino, Italy.
3
Molecular Imaging Center, University of Torino, Torino, Italy.
4
Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.
5
Department of Pathology, Children's Hospital Harvard Medical School, Boston, MA 02115, USA.
6
Department of Health Sciences, University of Milano-Bicocca, Milano, Italy.
7
Molecular Biotechnology Center, University of Torino, Torino, Italy.
8
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
9
Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
10
Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, MA 02115, USA.
#
Contributed equally

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.

PMID:
26419961
PMCID:
PMC4674335
DOI:
10.1158/2326-6066.CIR-15-0089
[Indexed for MEDLINE]
Free PMC Article

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