title: Adoptive immunotherapy with cytokine-induced killer cells generated with a new good manufacturing practice-grade protocol.
abstract: OBJECTIVE
  We have recently shown that thymoglobulin (TG) efficiently expands cytokine-induced killer (CIK) cells in combination with interferon (IFN)-γ and interleukin (IL)-2 (ITG2 protocol). It is presently unknown whether the infusion of autologous immune effector cells generated by TG, IFN-γ and IL-2 is feasible and safe.
  
  
  METHODS
  Five patients with advanced and/or refractory solid tumors were enrolled in the present phase I/II study. Peripheral blood mononuclear cells (PBMC) collected by leukapheresis were stimulated under good manufacturing practice (GMP)-conditions with IFN-γ, followed by TG and IL-2. After 2-3 weeks in culture, a median of 4.65 × 10(6) immune effector cells per kilogram of recipient's body weight was obtained and infused intravenously. The median time from enrollment into the study to infusion of the expanded CIK cells was 30 days.
  
  
  RESULTS
  ITG2 efficiently expanded immune effector cells that comprised both conventional natural killer (NK) cells and CD3(+) CD16(+) CD56(+) CIK cells. One patient with advanced melanoma died because of disease progression before the infusion of CIK cells. The target dose of at least 2.5 × 10(6) CIK cells/kg of recipient's body weight was reached in four out of five evaluable patients. CIK cells were administered intravenously without any measurable toxicity. In vitro, CIK cells exerted lytic activity against cervical cancer cells. The median survival was 4.5 months (range 1-13) from the first infusion of CIK cells.
  
  
  CONCLUSIONS
  This study has highlighted the feasibility and safety of the administration of CIK cells generated with the ITG2 protocol. Whether CIK cells can help control disease burden in patients with advanced malignancies will be determined in future clinical trials.
authors.affiliation: Department of Pediatric Hematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. sergio.rutella@opbg.net
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.forename: Paola
authors.initials: P
authors.lastname: Iudicone
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bonanno
authors.forename: Daniela
authors.initials: D
authors.lastname: Fioravanti
authors.forename: Annabella
authors.initials: A
authors.lastname: Procoli
authors.forename: Claudio
authors.initials: C
authors.lastname: Lavorino
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Foddai
authors.forename: Domenica
authors.initials: D
authors.lastname: Lorusso
authors.forename: Enrica
authors.initials: E
authors.lastname: Martinelli
authors.forename: Michele
authors.initials: M
authors.lastname: Vacca
authors.forename: Francesco
authors.initials: F
authors.lastname: Ipsevich
authors.forename: Marianna
authors.initials: M
authors.lastname: Nuti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Luca
authors.initials: L
authors.lastname: Pierelli
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000494:pharmacology; D002478:Cells, Cultured; D055612:Cytokine-Induced Killer Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007937:Leukapheresis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D008545:Melanoma / Q000097:blood / Q000628:therapy; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000628:therapy
chemical_list: D000961:Antilymphocyte Serum; D007376:Interleukin-2; D007371:Interferon-gamma; C512542:thymoglobulin