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

Dario Sangiolo, Giulia Mesiano, Loretta Gammaitoni, Valeria Leuci, Maja Todorovic, Lidia Giraudo, Cristina Cammarata, Carmine Dell'Aglio, Lorenzo D'Ambrosio, Alberto Pisacane, Ivana Sarotto, Sara Miano, Ivana Ferrero, Fabrizio Carnevale-Schianca, Ymera Pignochino, Francesco Sassi, Andrea Bertotti, Wanda Piacibello, Franca Fagioli, Massimo AgliettaGiovanni Grignani

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)119-129
Number of pages11
JournalCancer Research
Volume74
Issue number1
DOIs
Publication statusPublished - Jan 1 2014

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    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, I., Carnevale-Schianca, F., Pignochino, Y., Sassi, F., Bertotti, A., Piacibello, W., Fagioli, F., ... Grignani, G. (2014). Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas. Cancer Research, 74(1), 119-129. https://doi.org/10.1158/0008-5472.CAN-13-1559