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.
| Original language | English |
|---|---|
| Pages (from-to) | 119-129 |
| Number of pages | 11 |
| Journal | Cancer Research |
| Volume | 74 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2014 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas. / Sangiolo, Dario; Mesiano, Giulia; Gammaitoni, Loretta; Leuci, Valeria; Todorovic, Maja; Giraudo, Lidia; Cammarata, Cristina; Dell'Aglio, Carmine; D'Ambrosio, Lorenzo; Pisacane, Alberto; Sarotto, Ivana; Miano, Sara; Ferrero, Ivana; Carnevale-Schianca, Fabrizio; Pignochino, Ymera; Sassi, Francesco; Bertotti, Andrea; Piacibello, Wanda; Fagioli, Franca; Aglietta, Massimo; Grignani, Giovanni.
In: Cancer Research, Vol. 74, No. 1, 01.01.2014, p. 119-129.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas
AU - Sangiolo, Dario
AU - Mesiano, Giulia
AU - Gammaitoni, Loretta
AU - Leuci, Valeria
AU - Todorovic, Maja
AU - Giraudo, Lidia
AU - Cammarata, Cristina
AU - Dell'Aglio, Carmine
AU - D'Ambrosio, Lorenzo
AU - Pisacane, Alberto
AU - Sarotto, Ivana
AU - Miano, Sara
AU - Ferrero, Ivana
AU - Carnevale-Schianca, Fabrizio
AU - Pignochino, Ymera
AU - Sassi, Francesco
AU - Bertotti, Andrea
AU - Piacibello, Wanda
AU - Fagioli, Franca
AU - Aglietta, Massimo
AU - Grignani, Giovanni
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84892759435&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892759435&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-13-1559
DO - 10.1158/0008-5472.CAN-13-1559
M3 - Article
C2 - 24356422
AN - SCOPUS:84892759435
VL - 74
SP - 119
EP - 129
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 1
ER -