title: Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12.
abstract: BACKGROUND
  Vaccination with fusion cells (FCs) comprising dendritic cells and tumour cells as well as administration of interleukin-12 (IL-12) showed a significant therapeutic effect against established tumours in mouse experimental models. We conducted immunotherapy against various malignant tumours using the FCs and rhIL-12, and investigated the safety and efficacy of the therapy.
  
  
  METHODS
  Patients' DCs were mixed with autologous irradiated tumour cells and treated with 50% polyethylene glycol to generate FCs. The FCs were inoculated intradermally, and then 30 ng kg(-1) of rhIL-12 was injected at the same sites 2 and 6 days later. This process was carried out as one cycle, and three of these cycles were repeated at 1-week intervals to comprise one course. After completing the course, its safety and therapeutic effects were estimated.
  
  
  RESULTS
  The most frequently observed adverse event was fever, observed in 26% of patients in the first cycle. Decrease in white blood cell and an increase in serum ALT were observed in 28% and 25%, respectively. Three out of 12 patients with a malignant brain tumour (25%) achieved a partial response (PR), but other patients with a malignant tumour showed no regression of their tumours. Thirteen out of 16 patients with a brain tumour (81%) showed cutaneous delayed hypersensitivity responses. However, only one of 16 patients (6%) with a malignant tumour other than a brain tumour developed such responses.
  
  
  CONCLUSIONS
  Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour.
authors.affiliation: Jikei University School of Medicine, Tokyo, Japan. sahya@jikei.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Homma
authors.forename: T
authors.initials: T
authors.lastname: Kikuchi
authors.forename: N
authors.initials: N
authors.lastname: Ishiji
authors.forename: K
authors.initials: K
authors.lastname: Ochiai
authors.forename: H
authors.initials: H
authors.lastname: Takeyama
authors.forename: H
authors.initials: H
authors.lastname: Saotome
authors.forename: Y
authors.initials: Y
authors.lastname: Sagawa
authors.forename: E
authors.initials: E
authors.lastname: Hara
authors.forename: D
authors.initials: D
authors.lastname: Kufe
authors.forename: J L
authors.initials: JL
authors.lastname: Ryan
authors.forename: T
authors.initials: T
authors.lastname: Ohno
authors.forename: G
authors.initials: G
authors.lastname: Toda
mesh_terms: D002459:Cell Fusion / Q000379:methods; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D018664:Interleukin-12 / Q000008:administration & dosage*; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D012867:Skin / Q000276:immunology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D018664:Interleukin-12