title: Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor.
abstract: OBJECTIVE
  Adoptive T-cell therapy with tumor-specific 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-specific 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 efficacy of this immunotherapeutic approach in phase I/II studies.
authors.affiliation: Dipartimento di Scienze Pediatriche, Università di Pavia, Italy. d.montagna@smatteo.pv.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Montagna
authors.forename: Ilaria
authors.initials: I
authors.lastname: Turin
authors.forename: Roberta
authors.initials: R
authors.lastname: Schiavo
authors.forename: Enrica
authors.initials: E
authors.lastname: Montini
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
authors.forename: Raffaella
authors.initials: R
authors.lastname: Villa
authors.forename: Simona
authors.initials: S
authors.lastname: Secondino
authors.forename: Ilaria
authors.initials: I
authors.lastname: Schiavetto
authors.forename: Laura
authors.initials: L
authors.lastname: Caliogna
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Virginia
authors.initials: V
authors.lastname: Libri
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Roberto
authors.initials: R
authors.lastname: Tonelli
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.forename: Paolo
authors.initials: P
authors.lastname: Pedrazzoli
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D016913:Blood Component Transfusion; D001859:Bone Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016219:Immunotherapy, Adoptive; D007558:Italy; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008212:Lymphocyte Depletion; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012509:Sarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D014182:Transplantation, Autologous
chemical_list: D000951:Antigens, Neoplasm