title: Immunological effects of granulocyte-macrophage colony-stimulating factor and autologous tumor vaccine in patients with renal cell carcinoma.
abstract: OBJECTIVE
  Biological therapy for renal cell carcinoma (RCC) uses agents that mobilize immune effector cells which are able to recognize and destroy cancer. We evaluated the effects of weekly then monthly autologous tumor vaccine combined with daily granulocyte macrophage-colony stimulating factor (GM-CSF) in patients with RCC as a method of stimulating antigen presenting cells.
  
  
  METHODS
  Eligible patients with pathological stage II to IV RCC were entered into this pilot study. Autologous tumor vaccine (0.5 to 1 x 107 irradiated tumor cells) admixed with 250 microg GM-CSF per vaccine was given subcutaneously weekly for 4 weeks and then monthly for 4 months. GM-CSF (125 microg/m2) was given subcutaneously for 13 days after vaccine injection 1 and injections 4 to 8. Treatment related tumor specific CD4 and CD8 positive T cell precursors were assessed.
  
  
  RESULTS
  A total of 22 patients were entered into this study. Patients were stratified by bulk of disease (group 1, 9 patients with micrometastatic disease, and group 2, 13 patients with macrometastatic disease). In general treatment was well tolerated. Of 9 patients in group 1 7 remained disease-free after nephrectomy. In group 2, 6 patients had stable (46.2%) and 7 patients had progressive disease (53.8%). Statistically significant treatment related increases in CD4 (p = 0.028) and CD8 (p = 0.018) positive tumor specific T cell precursors were observed for the entire group of patients. Changes in CD4 and CD8 positive precursors correlated significantly with each other (p = 0.0001). This correlation was seen in the 2 patient subpopulations as well (group 1 p = 0.003, group 2 p = 0.013). Patients with minimal disease, and with changes in CD4 and CD8 positive tumor specific T cell precursors greater than the median appeared to have an improved time to progression as well as a survival benefit.
  
  
  CONCLUSIONS
  GM-CSF and autologous vaccine can be given safely in combination to patients with renal cell cancer. We observed treatment related changes in tumor specific circulating lymphocyte populations.
authors.affiliation: Uro-Oncology Group, Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0001, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwaab
authors.forename: Christopher  P
authors.initials: C
authors.lastname: Tretter
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Gibson
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Cole
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schned
authors.forename: Robert
authors.initials: R
authors.lastname: Harris
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wallen
authors.forename: Jan L
authors.initials: JL
authors.lastname: Fisher
authors.forename: Mary G
authors.initials: MG
authors.lastname: Waugh
authors.forename: Debra
authors.initials: D
authors.lastname: Truman
authors.forename: Laura M
authors.initials: LM
authors.lastname: Stempkowski
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Crosby
authors.forename: John  A
authors.initials: J
authors.lastname: Heaney
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor