TY - JOUR
T1 - Antitumoral effects of attenuated Listeria monocytogenes in a genetically engineered mouse model of melanoma
AU - Vitiello, Marianna
AU - Evangelista, Monica
AU - Di Lascio, Nicole
AU - Kusmic, Claudia
AU - Massa, Annamaria
AU - Orso, Francesca
AU - Sarti, Samanta
AU - Marranci, Andrea
AU - Rodzik, Katarzyna
AU - Germelli, Lorenzo
AU - Chandra, Dinesh
AU - Salvetti, Alessandra
AU - Pucci, Angela
AU - Taverna, Daniela
AU - Faita, Francesco
AU - Gravekamp, Claudia
AU - Poliseno, Laura
N1 - Funding Information:
Acknowledgements The authors would like to thank all the Poliseno lab members for their insightful discussions; S. Burchielli (FTGM, Pisa) for her assistance with animal procedures; D. Colecchia (IFC-CNR, ISPRO, Siena) for his assistance in preparing the figures; M. La Ferla (Fondazione Pisana per la Scienza, Pisa) for his assistance with the detection of listeria by FACS; G. Pelosi (IFC-CNR, Pisa) for his assistance with light microscopy; A. Ripoli (IFC-CNR, Pisa) for his support with statistical analyses; B. Stecca (ISPRO, Firenze) for providing us with the AldefluorTM kit. This work was supported by MFAG #17095 grant awarded by Associazione Italiana per la Ricerca sul Cancro (AIRC) to LP; start up funding awarded by ITT-Istituto Toscano Tumori and ISPRO-Istituto per lo Studio, la Prevenzione e la Rete Oncologica to LP. It was also supported by GR-2011-02348535 grant awarded by Italian Ministry of Health to LP. MV was supported by an EMBO short-term fellowship and an AIRC fellowship.
Publisher Copyright:
© 2019, The Authors.
PY - 2019/5/9
Y1 - 2019/5/9
N2 - Attenuated Listeria monocytogenes (Lmat-LLO) represents a valuable anticancer vaccine and drug delivery platform. Here we show that in vitro Lmat-LLO causes ROS production and, in turn, apoptotic killing of a wide variety of melanoma cells, irrespectively of their stage, mutational status, sensitivity to BRAF inhibitors or degree of stemness. We also show that, when administered in the therapeutic setting to Braf/Pten genetically engineered mice, Lmat-LLO causes a strong decrease in the size and volume of primary melanoma tumors, as well as a reduction of the metastatic burden. At the molecular level, we confirm that the anti-melanoma activity exerted in vivo by Lmat-LLO depends also on its ability to potentiate the immune response of the organism against the infected tumor. Our data pave the way to the preclinical testing of listeria-based immunotherapeutic strategies against metastatic melanoma, using a genetically engineered mouse rather than xenograft models.
AB - Attenuated Listeria monocytogenes (Lmat-LLO) represents a valuable anticancer vaccine and drug delivery platform. Here we show that in vitro Lmat-LLO causes ROS production and, in turn, apoptotic killing of a wide variety of melanoma cells, irrespectively of their stage, mutational status, sensitivity to BRAF inhibitors or degree of stemness. We also show that, when administered in the therapeutic setting to Braf/Pten genetically engineered mice, Lmat-LLO causes a strong decrease in the size and volume of primary melanoma tumors, as well as a reduction of the metastatic burden. At the molecular level, we confirm that the anti-melanoma activity exerted in vivo by Lmat-LLO depends also on its ability to potentiate the immune response of the organism against the infected tumor. Our data pave the way to the preclinical testing of listeria-based immunotherapeutic strategies against metastatic melanoma, using a genetically engineered mouse rather than xenograft models.
UR - http://www.scopus.com/inward/record.url?scp=85060330571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060330571&partnerID=8YFLogxK
U2 - 10.1038/s41388-019-0681-1
DO - 10.1038/s41388-019-0681-1
M3 - Article
C2 - 30664692
AN - SCOPUS:85060330571
SN - 0950-9232
VL - 38
SP - 3756
EP - 3762
JO - Oncogene
JF - Oncogene
IS - 19
ER -
