Antitumoral effects of attenuated Listeria monocytogenes in a genetically engineered mouse model of melanoma

Attenuated Listeria monocytogenes (Lm at -LLO) represents a valuable anticancer vaccine and drug delivery platform. Here we show that in vitro Lm at -LLO causes ROS production and, in turn, apoptotic killing of a wide variety of melanoma cells, irrespectively of their stage, mutational status, sensi...

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Bibliographic Details
Published in:Oncogene 2019-05, Vol.38 (19), p.3756-3762
Main Authors: Vitiello, Marianna, Evangelista, Monica, Di Lascio, Nicole, Kusmic, Claudia, Massa, Annamaria, Orso, Francesca, Sarti, Samanta, Marranci, Andrea, Rodzik, Katarzyna, Germelli, Lorenzo, Chandra, Dinesh, Salvetti, Alessandra, Pucci, Angela, Taverna, Daniela, Faita, Francesco, Gravekamp, Claudia, Poliseno, Laura
Format: Article
Language:English
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Animal models
Animals
Antineoplastic agents
Apoptosis
Brief Communication
Cancer cells
Cancer metastasis
Cancer treatment
Cancer vaccines
Cancer Vaccines - pharmacology
Cell Biology
Drug delivery
Drug delivery systems
Genetic aspects
Genetic engineering
Genetically modified organisms
Human Genetics
Immune response
Immunotherapy
Internal Medicine
Laboratory rats
Listeria
Listeria monocytogenes
Listeria monocytogenes - immunology
Medical schools
Medicine
Medicine & Public Health
Melanoma
Melanoma, Experimental - drug therapy
Melanoma, Experimental - genetics
Melanoma, Experimental - pathology
Metastases
Metastasis
Mice, Transgenic
Oncology
PTEN protein
Tumors
Vaccines
Vaccines, Attenuated - pharmacology
Vemurafenib
Xenografts
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Summary:Attenuated Listeria monocytogenes (Lm at -LLO) represents a valuable anticancer vaccine and drug delivery platform. Here we show that in vitro Lm at -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, Lm at -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 Lm at -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.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-019-0681-1