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    MVA-5T4-induced immune responses are an early marker of efficacy in renal cancer patients.

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    Authors
    Harrop, R
    Shingler, W H
    McDonald, M
    Treasure, P
    Amato, R J
    Hawkins, Robert E
    Kaufman, H L
    de Belin, J
    Kelleher, M
    Goonewardena, M
    Naylor, S
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    Affiliation
    Oxford BioMedica (UK) Ltd, The Medawar Centre, Oxford Science Park, Oxford, OX4 4GA, UK.
    Issue Date
    2011-06
    
    Metadata
    Show full item record
    Abstract
    Few immunotherapy compounds have demonstrated a direct link between the predicted mode of action of the product and benefit to the patient. Since cancer vaccines are thought to have a delayed therapeutic effect, identification of the active moiety may enable the development of an early marker of efficacy. Patients with renal cancer and requiring first-line treatment for metastatic disease were randomized 1:1 to receive MVA-5T4 (TroVax(®)) or placebo alongside Sunitinib, IL-2 or IFN-α in a multicentre phase III trial. Antibody responses were quantified following the 3rd and 4th vaccinations. A surrogate for 5T4 antibody response (the immune response surrogate; IRS) was constructed and then used in a survival analysis to evaluate treatment benefit. Seven hundred and thirty-three patients were randomized, and immune responses were assessed in 590 patients. A high 5T4 antibody response was associated with longer survival within the MVA-5T4-treated group. The IRS was constructed as a linear combination of pre-treatment 5T4 antibody levels, hemoglobin and hematocrit and was shown to be a significant predictor of treatment benefit in the phase III study. Importantly, the IRS was also associated with antibody response and survival in an independent dataset comprising renal, colorectal and prostate cancer patients treated with MVA-5T4 in phase I-II studies. The derivation of the IRS formed part of an exploratory, retrospective analysis; however, if confirmed in future studies, the results have important implications for the development and use of the MVA-5T4 vaccine and potentially for other similar vaccines.
    Citation
    MVA-5T4-induced immune responses are an early marker of efficacy in renal cancer patients. 2011, 60 (6):829-37 Cancer Immunol. Immunother.
    Journal
    Cancer Immunology, Immunotherapy
    URI
    http://hdl.handle.net/10541/201096
    DOI
    10.1007/s00262-011-0993-7
    PubMed ID
    21387109
    Type
    Article
    Language
    en
    ISSN
    1432-0851
    ae974a485f413a2113503eed53cd6c53
    10.1007/s00262-011-0993-7
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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