title: Results of a pilot trial of immunotherapy with dendritic cells pulsed with autologous tumor lysates in patients with advanced cancer.
abstract: OBJECTIVE
  The purpose of the study was to test the immunological and clinical effects of infusions of dendritic cells pulsed with autologous tumor lysate in patients with advanced cancer.
  
  
  METHODS
  Peripheral blood mononuclear cells from 15 patients with metastatic cancer (melanoma in 10, lung cancer in 2, renal cell carcinoma in 1, sarcoma in 1, breast cancer in 1) were harvested by leukapheresis after mobilization with GM-CSF (5 microg/kg/day s.c. for 4 days). Mononuclear cells were separated and cultured in GM-CSF (1000 U/ml) and interleukin-4 (1000 U/ml) for 7 days. Phenotype was assessed by 2-color flow cytometry and immunocytochemistry. On day 6, dendritic cells were pulsed with 1 g of fresh autologous tumor lysate for 24 h and infused intravenously. Interleukin-2 (6 million IU), interferon a (4 million IU) and GM-CSF (400 microg) were injected s.c. daily for 10 days beginning on the day of dendritic cell infusion. Treatment was repeated every 21 days for 3 courses.
  
  
  RESULTS
  The morphology, immunocytochemistry and phenotype of cultured cells was consistent with dendritic cells: intense positivity for HLA-DR and CD86, with negativity for markers of other lineages, including CD3, CD4, CD8 and CD14. More than 5 x 10(7) dendritic cells were injected in all patients. Nine patients developed >5 mm delayed type cutaneous hypersensitivity reactions to tumor lysate+/-GM-CSF after the first immunization (larger than GM-CSF in all cases). Median delayed type cutaneous hypersensitivity to lysate +/- GM-CSF was 3 cm after the third immunization. One melanoma patient with skin, liver, lung and bone metastases had a partial response lasting 8 months (followed by progression in the brain). Seven patients had stable disease for >3 months, and 7 had progression.
  
  
  CONCLUSIONS
  Infusion of tumor lysate-pulsed dendritic cells induces a strong cell-mediated antitumor immune reaction in patients with advanced cancer and has some clinical activity.
authors: Division of Medical Oncology,University Hospital, Zaragoza. josemayordomo@hotmail.com
authors: Jose Ignacio
authors: JI
authors: Mayordomo
authors: Raquel
authors: R
authors: Andres
authors: Maria Dolores
authors: MD
authors: Isla
authors: Laura
authors: L
authors: Murillo
authors: Rosana
authors: R
authors: Cajal
authors: Alfonso
authors: A
authors: Yubero
authors: Carmen
authors: C
authors: Blasco
authors: Pilar
authors: P
authors: Lasierra
authors: Luis
authors: L
authors: Palomera
authors: Miguel Angel
authors: MA
authors: Fuertes
authors: Antonio
authors: A
authors: Güemes
authors: Ramon
authors: R
authors: Sousa
authors: Maria Dolores
authors: MD
authors: Garcia-Prats
authors: Pilar
authors: P
authors: Escudero
authors: Alberto
authors: A
authors: Saenz
authors: Javier
authors: J
authors: Godino
authors: Ivan
authors: I
authors: Marco
authors: Berta
authors: B
authors: Saez
authors: Carmen
authors: C
authors: Visus
authors: Laura
authors: L
authors: Asin
authors: Gabriel
authors: G
authors: Valdivia
authors: Luis
authors: L
authors: Larrad
authors: Alejandro
authors: A
authors: Tres
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006968:Hypersensitivity, Delayed; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010865:Pilot Projects; D014182:Transplantation, Autologous
chemical_list: D015703:Antigens, CD