Cancer Immunology, Immunotherapy

, Volume 54, Issue 9, pp 848–857 | Cite as

Phase I study of TNFα AutoVaccIne in Patients with metastatic cancer

  • A. M. Waterston
  • L. Gumbrell
  • T. Bratt
  • S. Waller
  • J. Gustav-Aspland
  • C L‘Hermenier
  • K Bellenger
  • M Campbell
  • T Powles
  • M Highley
  • M Bower
  • S. Mouritsen
  • M. Feldmann
  • R. C. Coombes
Original Article

Abstract

We evaluated the safety and immunogencity of a novel vaccine directed against autologous TNFα in a Phase I fixed dose escalation trial. The vaccine consisted of two recombinant TNFα proteins, with specific peptides replaced by foreign immunodominant T cell epitopes from tetanus toxoid. The main objectives were to establish a safe dose and evaluate the vaccines ability to raise neutralising TNFα antibodies. Secondary objectives were improvements in body weight and tumour response. Thirty-three patients were vaccinated with three doses (20, 100, or 400 μg) of TNFα vaccine at 2-weekly intervals adjuvanted with aluminium hydroxide. Anti-TNFα antibody titres were measured by both a RIA, using soluble native TNFα as the antigen, and by an ELISA using immobilized partly denatured TNFα. Eleven patients (33%) had mild grade1/2 injection site reactions at the higher doses. In 10 of 20 patients, serum antibodies recognize denatured TNFα in the ELISA, whereas, antibody titres against native TNFα in the RIA were undetectable. This suggests that the production process had partly denatured the vaccine preventing the formation of cross-reacting antibodies to native TNFα. In conclusion, TNFα vaccine was able to elicit vaccine specific antibodies. However, since the antibodies were only able to cross-react with partly denatured TNFα, evaluation of safety and tumour responses to the TNFα vaccine was compromised.

Keywords

Tumour necrosis factorα TNFα Vaccine Autoantibodies Cancer 

Notes

Acknowledgements

We wish to thank Ferring Pharmaceutical for the funding of this Trial and Pharmexa for developing the vaccine and providing valuable advice, as well as Cancer Research (UK), who conducted the trial.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • A. M. Waterston
    • 1
    • 7
  • L. Gumbrell
    • 3
  • T. Bratt
    • 4
  • S. Waller
    • 3
  • J. Gustav-Aspland
    • 1
  • C L‘Hermenier
    • 1
  • K Bellenger
    • 3
  • M Campbell
    • 3
  • T Powles
    • 1
  • M Highley
    • 5
  • M Bower
    • 6
  • S. Mouritsen
    • 4
  • M. Feldmann
    • 2
  • R. C. Coombes
    • 1
  1. 1.Department of Cancer Medicine, Faculty of MedicineImperial college School of MedicineLondonUK
  2. 2.Kennedy Institute of Rheumatology Division, Faculty of MedicineImperial college School of MedicineLondonUK
  3. 3.Cancer Research UKLondonUK
  4. 4.Pharmexa A/SHorsholmDenmark
  5. 5.Department of Cancer MedicineNinewells HospitalDundeeUK
  6. 6.Chelsea and Westminster HospitalLondonUK
  7. 7.Department of Medical Oncology, Beatson Oncology CentreWestern InfirmaryGlasgow

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