Dario Sangiolo, M.D.
Immunotherapy with Cytokine-Induced Killer (CIK) cells for the treatment of solid tumors refractory to conventional treatments.
Adoptive immunotherapy holds promise for the treatment of solid tumors. Disease relapse and drug-resistance are sustained by a subset of putative cancer stem cells (CSC), poorly responsive to conventional treatments. Immunotherapy is a promising approach capable of targeting putative CSC. Our group has focused over the last years on a subset of T lymphocytes known as Cytokine-induced Killer (CIK) cells. CIK cells are ex vivo expanded T lymphocytes generated from circulating mononuclear cells, endowed with MHC-independent antitumor activity. The aim of our research is to explore adoptive immunotherapy with CIK cells for sarcomas and melanomas.
We demonstrated that immunotherapy with CIK cells is active against autologous sarcomas and melanomas, including putative CSC. Our main findings are summarized as follows. (i) Generation of CIK cells: clinically relevant rates of CIK cells were successfully expanded from patients with sarcomas and melanomas; (ii) tumor killing activity: patient-derived CIK cells were highly active against autologous sarcomas and melanomas pretreated with conventional chemotherapy; (iii) activity against CSC: we developed a gene-transfer strategy capable of visualizing putative CSC based on their ability to re-activate stem gene Oct4. Sarcoma and melanoma CSC were relatively resistant to conventional chemotherapy but susceptible to immunotherapy with CIK cells; iv) In preliminary experiments we demonstrated the possibility to redirect CIK cells with a chimeric-antigen receptor (CAR) against a precise target expressed in soft tissue sarcomas.
Conclusions and perspectives:
Adoptive immunotherapy with CIK cells is potentially active against solid tumors and capable of eradicating chemoresistant CSC. We plan to enhance the antitumor activity of CIK cells by their genetic redirection against tumor-specific targets. Furthermore we will explore synergism of immunotherapy with molecular targeted approaches.