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

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.

• Authors: Robert J Amato, William Shingler, Stuart Naylor, Jaroslaw Jac, James Willis, Somyata Saxena, Joan Hernandez-McClain, Richard Harrop
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 22 Pg. 7504-10 (Nov 15 2008) ISSN: 1078-0432 [Print] United States
• PMID: 19010868 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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