Immuno-biotherapy of melanoma and solid tumors
Treatment options for patients affected by advanced-stage metastatic tumors (melanoma, lung cancer, kidney cancer, etc.) have changed dramatically in the past six years, with the approval of new antitumor therapies based on the stimulation of the immune system. These treatments have indeed increased the overall survival of patients affected by histologically different tumors (melanoma, lung tumors, etc.). However, there are still many patients relapsing after an initial clinical benefit. Therefore, there is an urgent need to identify new evasion mechanisms adopted by tumors to escape immune cells, in order to increase the efficacy of antitumor treatments. The research activity of the Unit of immuno- biotherapy of melanoma and solid tumors is focused on the investigation of new tumor immune escape mechanisms.
Currently, the unit is investigating the cellular and molecular mechanisms by which oxysterols are generated and inactivated during the inflammation associated to cancer.
In addition, researchers of this group are characterizing, in different tumor models, molecules interfering with the LXR/oxysterol axis in order to potentiate antitumor immune responses.
Moresco MA, Raccosta L, Corna G, Maggioni D, Soncini M, Bicciato S, Doglioni C and Russo V. Enzymatic inactivation of oxysterols in breast tumor cells constraints metastasis formation by reprogramming the metastatic lung microenvironment. Front Immunol. 2018 Oct 2;9:2251.
Marinozzi M, Castro Navas FF, Fontana R, Maggioni D, Carosati E, Bocci G, Carloncelli M, Giorgi G, Cruciani G and Russo V. Side-Chain Modified Ergosterol and Stigmasterol Derivatives as Liver X Receptor Agonists. J Med Chem. 2017
Russo V, Amadori A, Bregni M, Calabrò L, Colombo MP, Di Nicola M, Ferrucci PF, Proietti E, Maio M and Bellone M. Goals and objectives of the Italian Network for Tumor Biotherapy (NIBIT). Cytokine Growth Factor Rev. 2017 Jun 16. pii: S1359- 6101(17)30070-9.
Soncini M, Corna G, Moresco M, Coltella N, Restuccia U, Maggioni D, Raccosta L, Lin C-Y, Invernizzi F, Crocchiolo R, Doglioni C, Traversari C, Bachi A, Bernardi R, Bordignon C, Gustafsson, J-A and Russo V. 24- Hydroxycholesterol participates in pancreatic neuroendocrine tumor development. Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6219-E6227.
Parmiani G, Pilla L, Corti A, Doglioni C, Cimminiello C, Bellone M, Parolini D, Russo V, Capocefalo F, Maccalli C. A pilot phase I study combining peptide- based vaccination and NGR-hTNF vessel targeting therapy in metastatic melanoma. Oncoimmunology. 2014 Dec 21;3(11):e963406.
Raccosta L, Fontana R, Maggioni D, Lanterna C, Villablanca EJ, Paniccia A, Musumeci A, Chiricozzi E, Trincavelli ML, Daniele S, Martini C, Gustafsson J-A, Doglioni C, Gonzalvo Feo S, Leiva A, Ciampa MG, Mauri L, Sensi C, Prinetti A, Eberini I, Mora JR, Bordignon C, Steffensen KR, Sonnino S, Sozzani S, Traversari C, Russo V. The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor promoting neutrophils. J Exp Med. 2013 Aug 26;210(9):1711-28.
Russo V, Pilla L, Lunghi F, Crocchiolo R, Greco R, Ciceri F, Maggioni D, Fontana R, Mukenge S, Rivoltini L, Rigamonti G, Mercuri SR, Nicoletti R, Maschio AD, Gianolli L, Fazio F, Marchianò A, Florio AD, Maio M, Salomoni M, Gallo-Stampino C, Fiacco MD, Lambiase A, Coulie PG, Patuzzo R, Parmiani G, Traversari C, Bordignon C, Santinami M, Bregni M. Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3- genetically modified lymphocytes. Int J Cancer. 2013 Jun 1;132(11):2557-66
Russo V, Bondanza A, Ciceri F, Bregni M, Bordignon C, Traversari C & Bonini C. Dual role of genetically modified lymphocytes in cancer immunotherapy. Trends Mol Med. 2012 Apr;18(4):193-200.
Villablanca EJ, Raccosta L, Zhou D, Fontana R, Maggioni D, Negro A, Sanvito F, Ponzoni M, Valentinis B, Bregni M, Prinetti A, Steffensen KR, Sonnino S, Gustafsson JA, Doglioni C, Bordignon C, Traversari C and Russo V. Tumor- mediated LXRα activation inhibits CCR7 expression on DC and dampens antitumor responses. Nat Med. 2010 Jan;16(1):98-105
Fontana R, Bregni M, Cipponi A, Raccosta L, Rainelli C, Maggioni D, Lunghi F, Ciceri F, Mukenge S, Doglioni C, Colau D, Coulie PG, Bordignon C, Traversari C and Russo V. Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients. Blood 2009;113:1651-60
Parmiani G, Russo V, Marrari A, Cutolo G, Casati C, Pilla L, Maccalli C, Rivoltini L, and Castelli C. Universal and stemness-related tumor antigen: potential use in cancer immunotherapy. Clinical Cancer Research. 13:5675-9, 2007
Russo V, Cipponi A, Raccosta L, Rainelli C, Fontana R, Maggioni D, Lunghi F, Mukenge S, Ciceri F, Bregni M, Bordignon C, Traversari C. Lymphocytes genetically modified to express tumor antigens target DCs in vivo and induce antitumor immunity. Journal of Clinical Investigation 2007;117:3087-96
Schultz E.S., Chapiro J., Lurquin C., Claverol S., Burlet-Schiltz O., Warnier G., Russo V., Morel S., Levy F., Boon T., Van den Eynde B.J., and van der Bruggen, P. The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA - B40 requires the immunoproteasome. J. Exp.Med.195,1-10; 2002
Russo V., Zhou D., Sartirana C., Rovere P., Villa A., Rossini S., Traversari C. and Bordignon C. Acquisition of intact allogeneic HLA molecules by human dendritic cells. Blood 11: 3473-3477, 2000
Russo V, Tanzarella S, Dalerba P, Rigatti D, Rovere P, Villa A, Bordignon C, Traversari C. Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I restricted T cell response. Proc. Natl. Acad. Sci. 2000;97: 2185-2190