Molecular Virology. Coordinator: Menotti

Engineering, characterization and optimization of oncolytic herpes simplex viruses retargeted to tumor receptors for cancer virotherapy. Virus-host interactions: morphological and functional alterations induced by HSV infection on cellular structures

Research themes

Anticancer therapies: engineering of herpesviral oncolytic vectors retargeted to tumor receptors for cancer virotherapy. Recombinant viruses harbor a modified envelope glycoprotein gD where a single chain antibody (scFv) specific for tumor receptors is inserted in two different positions. The prototypes of the recombinant viruses we generated are retargeted to HER2 (mammary and ovary tumors) and detargeted from natural receptors Nectin1 and HVEM (full retargeting). They showed oncolytic activity in vitro and in vivo in murine models of mammary and ovary tumors, and of HER2 over-expressing gliomas. In vivo experiments have been carried out in collaboration with Prof. Lollini (University of Bologna) and Prof. Malatesta (University of Genova). Recently we generated additional recombinant viruses: - retargeted to other tumor receptors (PSMA, prostate; EGFRvIII, glioma; EGFR, colon), - with enhanced cell-to-cell spread; - "armed" with immunomodulatory cytokines to favor tumor eradication with the host immune system contribution; - equipped with reporter genes suitable for a non-invasive monitoring of viral replication in vivo.

Virus-host interactions: morphological and functional alterations on cellular structures; analysis of cellular apoptotic responses; identification and analysis of protein-protein interactions involved in virus entry and egress.

Internship projects

For internship, please contact the group members via email.

  

Main Publications

Menotti L., Nicoletti G., Gatta V., Croci S., Landuzzi L., De Giovanni C., Nanni P., Lollini P.L., Campadelli-Fiume G. (2009). "Inhibition of human tumor growth in mice by an oncolytic herpes simplex virus designed to target solely HER-2-positive cells". Proc Natl Acad Sci USA 106: 9039-9044. http://www.ncbi.nlm.nih.gov/pubmed/19458262 

Campadelli-Fiume G., Menotti L., Avitabile E., Gianni T. (2012). "Viral and cellular contributions to herpes simplex virus entry into the cell". Curr Opin Virol 2: 28-36. http://www.ncbi.nlm.nih.gov/pubmed/22440963

Gambini E., Reisoli E., Appolloni I., Gatta V., Campadelli-Fiume G., Menotti L., Malatesta P. (2012). "Replication-competent herpes simplex virus retargeted to HER2 as therapy for high-grade glioma". Mol Ther 20: 994-1001. http://www.ncbi.nlm.nih.gov/pubmed/22354378

Menotti L, Avitabile E, Gatta V, Malatesta P, Petrovic B, Campadelli-Fiume G. (2018). "HSV as A Platform for the Generation of Retargeted, Armed, and Reporter-Expressing Oncolytic Viruses". Viruses 1: E352. https://www.ncbi.nlm.nih.gov/pubmed/29966356

Alessandrini F, Menotti L, Avitabile E, Appolloni I, Ceresa D, Marubbi D, Campadelli-Fiume G, Malatesta P. (2019). "Eradication of glioblastoma by immuno-virotherapy with a retargeted oncolytic HSV in a preclinical model". Oncogene. 38:4467-4479. https://www.ncbi.nlm.nih.gov/pubmed/30755732

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