title: Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.
abstract: Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease.
authors.affiliation: Authors' Affiliations: Stem Cell Transplantation and Cell Therapy, Pathology, Sarcoma, Fondazione del Piemonte per l'Oncologia, Laboratory of Molecular Pharmacology, Institute for Cancer Research and Treatment; Department of Oncology, University of Torino Medical School; and Division of Pediatric Onco-Hematology, Sant'Anna OIRM Hospital, (Torino), Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Sangiolo
authors.forename: Giulia
authors.initials: G
authors.lastname: Mesiano
authors.forename: Loretta
authors.initials: L
authors.lastname: Gammaitoni
authors.forename: Valeria
authors.initials: V
authors.lastname: Leuci
authors.forename: Maja
authors.initials: M
authors.lastname: Todorovic
authors.forename: Lidia
authors.initials: L
authors.lastname: Giraudo
authors.forename: Cristina
authors.initials: C
authors.lastname: Cammarata
authors.forename: Carmine
authors.initials: C
authors.lastname: Dell'Aglio
authors.forename: Lorenzo
authors.initials: L
authors.lastname: D'Ambrosio
authors.forename: Alberto
authors.initials: A
authors.lastname: Pisacane
authors.forename: Ivana
authors.initials: I
authors.lastname: Sarotto
authors.forename: Sara
authors.initials: S
authors.lastname: Miano
authors.forename: Ivana
authors.initials: I
authors.lastname: Ferrero
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carnevale-Schianca
authors.forename: Ymera
authors.initials: Y
authors.lastname: Pignochino
authors.forename: Francesco
authors.initials: F
authors.lastname: Sassi
authors.forename: Andrea
authors.initials: A
authors.lastname: Bertotti
authors.forename: Wanda
authors.initials: W
authors.lastname: Piacibello
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grignani
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012509:Sarcoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
chemical_list: D016207:Cytokines