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Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses

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Abstract

Modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax®) has been evaluated in an open label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during and after treatment with 5-fluorouracil, leukovorin and irinotecan. TroVax was administered to 19 patients with metastatic colorectal cancer. Twelve patients had blood samples taken following each of the six injections and were considered to be evaluable for assessment of immunological responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector MVA were monitored throughout the study. Administration of TroVax alongside chemotherapy was safe and well tolerated with no SAEs attributed to the vaccine and no enhancement of chemo-related toxicity. Of the 12 patients who were evaluable for assessment of immune responses, ten mounted 5T4-specific antibody responses with titers ranging from 10 to >5,000. IFNγ ELISPOT responses specific for 5T4 were detected in 11 patients with frequencies exceeding one in 1,000 PBMCs in five patients. Eight patients presented with elevated circulating CEA concentrations, six of whom showed decreases in excess of 50% during chemotherapy and four had CEA levels which remained stable for >1 month following completion of chemotherapy. Of the 19 intention to treat (ITT) patients, one had a CR, six had PRs and five had SD. Potent 5T4-specific cellular and/or humoral immune responses were induced in all 12 evaluable patients and were detectable in most patients during the period in which chemotherapy was administered. These data demonstrate that TroVax can be layered on top of chemotherapy regimens without any evidence of enhanced toxicity or reduced immunological or therapeutic efficacy.

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Author notes

  1. Miles W. Carroll

    Present address: R2D Ltd, 6 Newbury Street, Wantage, OX12 8BS, UK

Authors and Affiliations

  1. Oxford BioMedica (UK) Ltd, The Medawar Centre, Oxford Science Park, Oxford, OX4 4GA, UK

    Richard Harrop, Noel Drury, William Shingler, Priscilla Chikoti, Irina Redchenko, Miles W. Carroll, Susan M. Kingsman & Stuart Naylor

  2. The Christie Hospital, Withington, Manchester, M20 3BX, UK

    Richard Griffiths & Robert E. Hawkins

  3. Queen Elizabeth Hospital, Birmingham, B15 2TT, UK

    Neil Steven

Authors
  1. Richard Harrop
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  2. Noel Drury
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  3. William Shingler
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  4. Priscilla Chikoti
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  5. Irina Redchenko
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  6. Miles W. Carroll
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  7. Susan M. Kingsman
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  8. Stuart Naylor
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  9. Richard Griffiths
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  10. Neil Steven
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  11. Robert E. Hawkins
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Correspondence to Richard Harrop.

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Harrop, R., Drury, N., Shingler, W. et al. Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses. Cancer Immunol Immunother 57, 977–986 (2008). https://doi.org/10.1007/s00262-007-0428-7

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  • DOI: https://doi.org/10.1007/s00262-007-0428-7

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