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 mousemodels. 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.

Voena, C., Menotti, M., Mastini, C., Di Giacomo, F., Longo, D., Castella, B., et al. (2015). Efficacy of a cancer vaccine against ALK-rearranged lung tumors. CANCER IMMUNOLOGY RESEARCH, 3(12), 1333-1343 [10.1158/2326-6066.CIR-15-0089].

Efficacy of a cancer vaccine against ALK-rearranged lung tumors

MASTINI, CRISTINA;MOLOGNI, LUCA;
2015

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 mousemodels. 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.
Articolo in rivista - Articolo scientifico
ALK, vaccine, crizotinib, ALCL
English
2015
3
12
1333
1343
open
Voena, C., Menotti, M., Mastini, C., Di Giacomo, F., Longo, D., Castella, B., et al. (2015). Efficacy of a cancer vaccine against ALK-rearranged lung tumors. CANCER IMMUNOLOGY RESEARCH, 3(12), 1333-1343 [10.1158/2326-6066.CIR-15-0089].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/108399
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