title: Vaccination of renal cell cancer patients with modified vaccinia ankara delivering tumor antigen 5T4 (TroVax) administered with interleukin 2: a phase II trial.
abstract: OBJECTIVE
  The attenuated vaccinia virus modified vaccinia ankara (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). TroVax has been evaluated in an open-label phase II trial in metastatic renal cell cancer patients in which the vaccine was administered in combination with interleukin-2 (IL-2). The safety, immunologic, and clinical efficacy of TroVax in combination with IL-2 was determined.
  
  
  METHODS
  Twenty-five patients with metastatic renal cell cancer were treated with TroVax plus IL-2. 5T4-specific cellular and humoral responses were monitored throughout the study. Clinical responses were assessed by measuring changes in tumor burden by computed tomography or magnetic resonance imaging scan.
  
  
  RESULTS
  TroVax was well tolerated with no serious adverse event attributed to vaccination. Of 25 intention-to-treat patients, 21 mounted 5T4-specific antibody responses. Two patients showed a complete response for > 24 months and one a partial response for > 12 months. Six patients had disease stabilization from 6 to > 21 months. Median progression-free survival (PFS) and overall survival (OS) were > 3.37 months (range, 1.50- > 24.76) and > 12.87 months (range, 1.90- > 24.76), respectively. A statistically significant relationship was detected between the magnitude of 5T4-specific antibody responses and PFS and OS.
  
  
  CONCLUSIONS
  TroVax in combination with IL-2 was safe and well tolerated in all patients. The high frequency of 5T4-specific immune responses and good clinical response rate are encouraging and warrant further investigation.
authors.affiliation: The Methodist Hospital Research Institute, Houston, Texas 77030, USA. ramato@tmhs.org
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Amato
authors.forename: William
authors.initials: W
authors.lastname: Shingler
authors.forename: Stuart
authors.initials: S
authors.lastname: Naylor
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Jac
authors.forename: James
authors.initials: J
authors.lastname: Willis
authors.forename: Somyata
authors.initials: S
authors.lastname: Saxena
authors.forename: Joan
authors.initials: J
authors.lastname: Hernandez-McClain
authors.forename: Richard
authors.initials: R
authors.lastname: Harrop
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; C504058:TroVax; D019444:Vaccines, DNA; C063709:trophoblastic glycoprotein 5T4, human