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

TitleEfficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors.
Publication TypeJournal Article
Year of Publication2015
AuthorsVoena C, Menotti M, Mastini C, Di Giacomo F, Longo DLivio, Castella B, Merlo MElena Bogg, Ambrogio C, Wang Q, Minero VGiacomo, Poggio T, Martinengo C, D'Amico L, Panizza E, Mologni L, Cavallo F, Altruda F, Butaney M, Capelletti M, Inghirami G, Jänne PA, Chiarle R
JournalCancer Immunol Res
Volume3
Issue12
Pagination1333-1343
Date Published2015 Dec
ISSN2326-6074
KeywordsAnaplastic Lymphoma Kinase, Animals, B7-H1 Antigen, Cancer Vaccines, Carcinoma, Non-Small-Cell Lung, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Crizotinib, Humans, Lung Neoplasms, Mice, Mice, Inbred BALB C, Mice, Transgenic, Programmed Cell Death 1 Receptor, Protein Kinase Inhibitors, Pyrazoles, Pyridines, Receptor Protein-Tyrosine Kinases, Tumor Microenvironment, Vaccination, Xenograft Model Antitumor Assays
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.

DOI10.1158/2326-6066.CIR-15-0089
Alternate JournalCancer Immunol Res
PubMed ID26419961
PubMed Central IDPMC4674335
Grant List242965 / / European Research Council / International
R01 CA136851 / CA / NCI NIH HHS / United States
R01 CA196703 / CA / NCI NIH HHS / United States
R01CA136851 / CA / NCI NIH HHS / United States
Related Faculty: 
Giorgio Inghirami, M.D.

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