Dendritic cell immunotherapy of glioblastoma multiforme

The Research

Finocchiaro G.

Current standard treatment of glioblastoma multiforme (GBM) is based on the surgical resection of the tumour mass followed by radio- and chemotherapy (Stupp et al., 2005). In spite of novel therapeutic approaches, the prognosis remains dismal and relapse is almost inevitable. We thus clearly need to produce long term, well tolerated and tumourspecific treatments able to eliminate the (remaining) tumour cells infiltrated in the nearby brain areas.
The immune system provides important tools in this direction. Preclinical trials for the development of vaccines against high-grade gliomas, based on the use of potent immune cells i.e. dendritic cells, exposed to a mix of tumour antigens deriving from the glioma (Pellegatta et al., 2005 and 2006), have been carried out in both rat models (Liau et al., 1999; Siesjo et al., 1996; Witham et al., 2002) and mouse models (Akasaki et al., 2001; Heimberger et al., 2000; Insug et al., 2002; Kikuchi et al., 2002; Ni et al., 2001; Okada et al., 1998), showing their capacity to produce a tumour-specific immune response.
Mature DC with autologous tumour lysate have been used to treat patients with relapsed malignant tumours (De Vleeschouwer et al., 2004; Rutkowski et al., 2004; Wheeler et al., 2004; Yamanaka et al., 2003; Yu et al., 2004); no significant adverse effects have been reported. In Italy we have been able to repeat this experience with the treatment of six patients affected by relapsing GBM, using dendritic cells prepared at the Istituto Neurologico Besta. Median survival of these patients from time of relapse is currently of 11,5 months (Finocchiaro et al, manuscript in preparation).
The results of the use of immunotherapy on GBM patients are promising, but further investigation is necessary to identify a safe and more effective combination of immunotherapy with radio- and chemotherapy after tumour resection.

Dott. Gaetano Finocchiaro, M.D.

Director, Unit Neurology 8- Molecular Neuro-Oncology
Director, Department of Neuro-Oncology
Fondazione IRCCS Istituto Neurologico Besta
via Celoria 11, 20133 Milano
Phone +39 02 2394 2769
fax +39 02 2394 2453

Group-leader IFOM-IEO Campus
via Adamello 16, 20139 Milano
Phone +39 02 9437 5113

E mail: finocchiaro@istituto-besta.it

Evolution

Serena Pellegatta, Barbara Savoldo, Natalia Di Ianni, Cristina Corbetta, Yuhui Chen, Monica Patané, Chuang Sun, Bianca Pollo, Soldano Ferrone, Francesco DiMeco, Gaetano Finocchiaro, Gianpietro Dotti
Constitutive and TNFα-inducible expression of chondroitin sulfate proteoglycan 4 in glioblastoma and neurospheres: Implications for CAR-T cell therapy.
Science Translational Medicine, 10, eaao2731 (2018) 28 February 2018.
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Serena Pellegatta, Marica Eoli, Valeria Cuccarini, Elena Anghileri, Bianca Pollo, Sara Pessina, Simona Frigerio, Maura Servida, Lucia Cuppini, Carlo Antozzi, Stefania Cuzzubbo, Cristina Corbetta, Rosina Paterra, Francesco Acerbi, Paolo Ferroli, Francesco DiMeco, Laura Fariselli, Eugenio A. Parati, Maria Grazia Bruzzone & Gaetano Finocchiaro
Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8+ T cell activation in the presence of adjuvant temozolomide
OncoImmunology, Volume 7, 2018 – Issue 4
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Serena Pellegatta, Pietro Luigi Poliani, Elena Stucchi, Daniela Corno, Chiara Agnese Colombo, Francesca Orzan, Maria Ravanini, and Gaetano Finocchiaro.
Intra-tumoral dendritic cells increase efficacy of peripheral vaccination by modulation of glioma microenvironment.
Neuro-Oncology 12(4) -377-388, 2010.
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Gabriele Cantini, Federica Pisati, Sara Pessina, Gaetano Finocchiaro and Serena Pellegatta.
Immunotherapy against the radial glia marker GLAST effectively triggers specific antitumor effectors without autoimmunity.
Oncoimmunology 1:6, 884-893; September 2012.
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Serena Pellegatta, Marica Eoli, Simona Frigerio, Carlo Antozzi, Maria Grazia Bruzzone, Gabriele Cantini, sara Nava, Elena Anghileri, Lucia Cuppini, Valeria Cuccarini, Emilio Ciusani, Marta Dossena, Bianca Pollo, Renato Mantegazza, Eugenio A. Parati and Gaetano Finocchiaro.
The natural killer cell response and tumor debulking are associated with prolonged serviva in recurrent glioblastoma patients receiving dendritic cells loaded with autologous tumor lysates.
Oncoimmunology 2:3, e23401; March 2013.
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Pellegatta S, Poliani PL, Corno D, Menghi F, Ghielmetti F, Suarez-Merino B, Caldera V, Nava S, Ravanini M, Facchetti F, Bruzzone MG, Finocchiaro G.
Neurospheres Enriched in Cancer Stem-Like Cells Are Highly Effective in Eliciting a Dendritic Cell-Mediated Immune Response against Malignant Gliomas.
Cancer Res. 2006 Nov 1;66(21):10247-52.
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Gabriele Cantini, Federica Pisati, Alfonso Mastropietro, Véronique Frattini, Yoichiro Iwakura, Gaetano Finocchiaro, Serena Pellegatta
A critical role for regulatory T cells in driving cytokines profiles of Th17 cells and their modulation of glioma microenvironment.
Cancer Immunol. Immunother. 2011 Jul DOI 10.1007/s00262-011-1069-4.
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Gabriele Cantini, Federica Pisati, Sara Pessina, Gaetano Finocchiaro and Serena Pellegatta
Immunotherapy against the radial glia marker GLAST effectively triggers specific antitumor effectors without autoimmunity
OncoImmunology 1:8, 1-10; November 2012; © 2012 Landes Bioscience.
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Véronique Frattini, Federica Pisati, Maria Carmela Speranza, Pietro Luigi Poliani, Gianmaria Frigé, Gabriele Cantini, Dimos Kapetis, Manuela Cominelli, Alessandra Rossi, Gaetano Finocchiaro and Serena Pellegatta
FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration
Oncotarget, Advance Publications, September 2012.
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Antonella De Rosa, Serena Pellegatta, Marco Rossi, Patrizia Tunici, Letizia Magnoni, Maria Carmela Speranza, Federico Malusa, Vincenzo Miragliotta, Elisa Mori, Gaetano Finocchiaro, Annette Bakker
A Radial Glia Gene Marker, Fatty Acid Binding Protein 7 (FABP7), Is Involved in Proliferation and Invasion of Glioblastoma Cells
PLOS ONE, December 2012, Volume 7, Issue 12, e52113.
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Sara Nava, Marta Dossena, Simona Pogliani, Serena Pellegatta, Carlo Antozzi, Fulvio Baggi, Cinzia Gellera, Bianca Pollo, Eugenio A. Parati, Gaetano Finocchiaro, Simona Frigerio
An Optimized Method for Manufacturing a Clinical Scale Dendritic Cell-Based Vaccine for the Treatment of Glioblastoma
PLOS ONE, December 2012, Volume 7, Issue 12, e52301.
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