Clinical Cell Therapy
Fabrizio Carnevale Schianca, MD
Hematopoietic Cell Transplantation (HCT): toward an immunological platform for cell and molecular therapy in the treatment of metastatic refractory cancers.
Allogeneic HCT, coupling to high dose chemotherapy a powerful donor immunological anti-tumoral effect, is a curative therapy for many hematological malignancies. However in the past years its broader application has been limited by two relevant obstacles: the first being represented by Graft versus host disease (GVHD) -the second being represented by the incapability of generating a specific graft versus tumor effect (GVT). Only when it will be possible to achieve a complete control of GVHD along with the generation of a specific GVT, allogeneic HCT will accomplish its extraordinary curative potential. Our research is focused on the clinical application of a strategy able to fully control GVHD and that transforms HCT into a safe platform for adoptive cell therapy.
In regard to GVHD our group contributed to the study of conventional treatment and classification of this complication and is currently running an interventional study of post-transplant cyclophosphamide (PT-CY) as a safe strategy for GVHD control. In this context in the first 30 patients treated we reported an extremely low rate of acute GVHD and no incidence of cGVHD. In regard to GVT (i) we at first revealed that following HCT it was possible to generate donor T cells specifically directed against patient-tumor antigens. (ii) We contributed to the demonstration that allogeneic HCT is an effective cell-therapy in the treatment of Multiple Myeloma. (iii) We have been involved in pre-clinical studies regardings to a specific form of cell-therapy derived from the generation and infusion of Cytokine-induced-Killer cells (CIK). In regard to Cell therapy regulatory issues and Law: cell therapy clinical application will be allowed only in Clinical centers that are JACIE-FACT accredited. Our Transplant center as part of the Turin metropolitan transplant network was accredited in July 2013.
Conclusions and perspectives:
The introduction in the clinical scenario of a safe strategy for GVHD control will allow HCT fully explored to be as a platform for tumor specific cell therapy and investigating if this platform might contribute to a future integration of cell therapy and molecular therapies. We plan to design and conduct clinical trials of cell-therapy (CIK and tumor specific T-cells) in the context of the Turin metropolitan transplant network both in solid tumors (melanoma and sarcomas) and in hematological malignancies.
Daniela Caravelli, M.D.