title: Phase II trial of autologous tumor vaccination, anti-CD3-activated vaccine-primed lymphocytes, and interleukin-2 in stage IV renal cell cancer.
abstract: OBJECTIVE
  Previous preclinical and clinical studies have demonstrated that autologous tumor vaccines can induce relatively specific tumor-reactive T cells in draining lymph nodes. The adoptive transfer of these cells can result in tumor regression.
  
  
  METHODS
  Patients with stage IV renal cell cancer (RCC) were vaccinated with irradiated autologous tumor cells admixed with Calmette-Guérin bacillus. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were harvested and the lymphoid cells secondarily activated with anti-CD3 monoclonal antibody and expanded in interleukin 2 (IL-2). The activated cells were subsequently infused intravenously along with the concomitant administration of bolus IL-2 (360,000 U/kg intravenously x 15 doses).
  
  
  RESULTS
  Thirty-nine patients were entered onto the study, of whom 34 completed an initial course of cell therapy consisting of a mean (SEM) number of 4.3 (2.2) x 10(10) VPLN cells. Among subjects who received cell therapy, there were nine responses (four complete responses [CRs] and five partial responses [PRs]), for an overall response rate of 27%. The durations of the CRs were > 48, 45, > 35, and 12 months, and the durations of the PRs were > 63, 48, 15, 12, and 4 months. Cultured tumor cells were available to assess in vitro cytokine release of VPLN cells in 24 subjects. The median cytokine release ratio of interferon gamma (IFNgamma) to IL-10 for responders and nonresponders was 992 and 5, respectively, which was significantly different (P =.047).
  
  
  CONCLUSIONS
  The treatment protocol resulted in durable tumor responses in patients with advanced RCC. The ratio of IFNgamma and IL-10 cytokines released in response to tumor by the VPLN cells was a significant correlate with tumor response.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, USA. aechang@umich.edu
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Chang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.forename: Guihua
authors.initials: G
authors.lastname: Jiang
authors.forename: Donna M
authors.initials: DM
authors.lastname: Sayre
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Braun
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Redman
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016219:Immunotherapy, Adoptive / Q000379:methods*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis; D009367:Neoplasm Staging; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D019496:Cancer Vaccines; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma