Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor

Autor: Virginia Libri, Nadia Zaffaroni, Enrica Montini, Raffaella Villa, Roberto Tonelli, Rita Maccario, Simona Secondino, Laura Caliogna, Salvatore Siena, Ilaria Schiavetto, Roberta Schiavo, Andrea Pession, Daniela Montagna, Franco Locatelli, Ilaria Turin, Paolo Pedrazzoli
Přispěvatelé: D MONTAGNA, I TURIN, R SCHIAVO, E MONTINI, N ZAFFARONI, R VILLA, S SECONDINO, I SCHIAVETTO, L CALIOGNA, F LOCATELLI, VIRGINIA LIBRI, ANDREA PESSION, R TONELLI, R MACCARIO, S SIENA, P PEDRAZZOLI
Rok vydání: 2012
Předmět:
Adult
Male
Cancer Research
Adoptive cell transfer
medicine.medical_treatment
Immunology
Blood Component Transfusion
Bone Neoplasms
Immunotherapy
Adoptive
Transplantation
Autologous
Peripheral blood mononuclear cell
Lymphocyte Depletion
Lymphocytes
Tumor-Infiltrating
Antigen
Antigens
Neoplasm
medicine
Humans
Immunology and Allergy
Cytotoxic T cell
Neuroectodermal Tumors
Primitive
Peripheral
ADOPTIVE T-CELL THERAPY
Neoplasm Metastasis
Carcinoma
Renal Cell
Genetics (clinical)
Aged
Ovarian Neoplasms
Transplantation
Chemotherapy
AUTOLOGOUS TUMOR CELLS
business.industry
Sarcoma
CYTOTOXIC T LYMPHOCYTES
Cell Biology
Immunotherapy
Middle Aged
SOLID TUMORS
Kidney Neoplasms
LYMPHODEPLETION
CTL
Italy
Oncology
Cancer research
Feasibility Studies
Female
business
Ex vivo
Follow-Up Studies
T-Lymphocytes
Cytotoxic
Zdroj: Cytotherapy. 14:80-90
ISSN: 1465-3249
DOI: 10.3109/14653249.2011.610303
Popis: Background aims. Adoptive T-cell therapy with tumor-specifi c T cells has emerged as a potentially useful approach for treating patients with advanced malignancies. We have demonstrated previously the feasibility of obtaining large numbers of autologous anti-tumor-specifi c cytotoxic T lymphocytes (CTL) generated by stimulation of patients ’ peripheral blood mononuclear cells with dendritic cells pulsed with apoptotic tumor cells. Methods . Six patients with progressing metastatic solid tumors (one renal cell carcinoma, two ovarian cancers, two extraosseous peripheral neuroectodermal tumors, one soft tissue sarcoma) not eligible for conventional therapies were treated with adoptive immunotherapy. Anti-tumor CTL, proven to be reactive in vitro against patient tumor cells, but not against normal cells, were infused following lymphodepleting chemotherapy administered to favor T-cell proliferation in vivo. Results . Patients received a median of nine CTL infusions (range 2 – 19). The median number of CTL administered per infusion was 11 10 8 (range 1 – 55 10 8 ). No patient experienced acute or late adverse events related to CTL infusion, even when large numbers of cells were given. Post-infusion laboratory investigations demonstrated an increase in the frequency of circulating anti-tumor T-cells and, in patients with a longer follow-up receiving two CTL infusions/year, a stabilization of these values. Conclusions. Our study demonstrates that autologous ex vivo -generated anti-tumor CTL can be administered safely in patients with advanced solid tumors and can improve the immunologic reactivity of recipients against tumor. These preliminary results provide a rationale for evaluating the clinical effi cacy of this immunotherapeutic approach in phase I/II studies.
Databáze: OpenAIRE
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