Vaccination of colorectal cancer patients with modified vaccinia Ankara delivering the tumour antigen 5T4 (TroVax) induces immune responses which correlates with disease control: a phase I/II trial

R Harrop, Noel Connolly, I Redchenko, J Valle, Mark Saunders, MG Ryan, KA Myers, N Drury, SM Kingsman, Robert Hawkins, MW Carroll

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The highly attenuated strain of vaccinia virus, modified vaccinia Ankara (MVA), encoding the tumor antigen 5T4 (termed TroVax), has been evaluated in an open-label phase I/II study in colorectal cancer patients. The primary objectives were to assess the safety and immunogenicity of ascending doses of TroVax and to determine the biodistribution of the vector.

Experimental Design: TroVax was given to 22 patients with metastatic colorectal cancer. Seventeen patients received doses of TroVax ranging from 5 × 107 up to 5 × 108 plaque-forming units at 0, 4, and 8 weeks and were considered to be evaluable for assessment of immunologic responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector were monitored throughout the study.

Results: TroVax was well tolerated in all patients with no serious adverse events attributed to vaccination. Of 17 evaluable patients, 16 showed 5T4-specific cellular responses whereas 14 had detectable antibody levels following vaccination. TroVax was able to boost 5T4-specific immune responses in the presence of MVA neutralizing antibodies. Periods of disease stabilization ranging from 3 to 18 months were observed in five patients, all of whom mounted 5T4-specific immune responses. Furthermore, statistical analysis showed a positive association between the development of a 5T4 (but not MVA) antibody response and patient survival or time to disease progression.

Conclusion: These data indicate that vaccination with TroVax is safe and well tolerated and that immune responses to 5T4 can be induced without any evidence of autoimmune toxicity. Furthermore, 5T4-specific antibody responses correlate with evidence of disease control.
Original languageEnglish
Pages (from-to)3416-3424
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number11 Pt 1
DOIs
Publication statusPublished - 1 Jun 2006

Keywords

  • administration & dosage: Adjuvants, Immunologic
  • Adult
  • Aged
  • Antigen-Antibody Reactions
  • administration & dosage: Antigens, Neoplasm
  • administration & dosage: Cancer Vaccines
  • drug effects: Cell Proliferation
  • immunology: Colorectal Neoplasms
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Toxicity
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • Vaccination

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