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. Cancer Res; 74(1); 119-29. ©2013 AACR.

Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.

SANGIOLO, Dario;D'Ambrosio L;FERRERO, Ivana;PIGNOCHINO, YMERA;BERTOTTI, Andrea;PIACIBELLO, Vanda;Fagioli F;AGLIETTA, Massimo;
2014-01-01

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. Cancer Res; 74(1); 119-29. ©2013 AACR.
2014
Jan 1;74
1
119
129
http://cancerres.aacrjournals.org/
Cytokine-induced killer cells; bone sarcomas; soft-tissue sarcomas
Sangiolo D; Mesiano G; Gammaitoni L; Leuci V; Todorovic M; Giraudo L; Cammarata C; Dell'aglio C; D'Ambrosio L; Pisacane A; Sarotto I; Miano S; Ferrero...espandi
File in questo prodotto:
File Dimensione Formato  
2014_Sangiolo et al_CAN RES.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 1.06 MB
Formato Adobe PDF
1.06 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Cancer Res 2014_Sangiolo D et al_CIK cell eradicate bone soft tissue sarcomas_4aperto.pdf

Open Access dal 02/01/2015

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 13.19 MB
Formato Adobe PDF
13.19 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/141017
Citazioni
  • ???jsp.display-item.citation.pmc??? 41
  • Scopus 65
  • ???jsp.display-item.citation.isi??? 60
social impact