Vaccination of renal cell cancer patients with modified vaccinia ankara delivering tumor antigen 5T4 (TroVax) administered with interleukin 2: a phase II trial

Clin Cancer Res. 2008 Nov 15;14(22):7504-10. doi: 10.1158/1078-0432.CCR-08-0668.

Abstract

Purpose: 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.

Experimental design: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / therapy*
  • Disease-Free Survival
  • Female
  • Humans
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / adverse effects
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / therapy*
  • Male
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Vaccination / adverse effects
  • Vaccination / methods
  • Vaccines, DNA
  • Vaccinia virus / immunology

Substances

  • Antineoplastic Agents
  • Cancer Vaccines
  • Interleukin-2
  • Membrane Glycoproteins
  • TroVax
  • Vaccines, DNA
  • trophoblastic glycoprotein 5T4, human