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Antivector and tumor immune responses following adenovirus-directed enzyme prodrug therapy for the treatment of prostate cancer
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Onion, David, Patel, Prashant, Pineda, Robert G., James, Nicholas D. and Mautner, Vivien (2009) Antivector and tumor immune responses following adenovirus-directed enzyme prodrug therapy for the treatment of prostate cancer. Human Gene Therapy, 20 (11). pp. 1249-1258. doi:10.1089/hum.2009.078 ISSN 1043-0342.
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Official URL: http://dx.doi.org/10.1089/hum.2009.078
Abstract
We have completed a phase I/II suicide gene therapy clinical trial in patients with prostate cancer, using an E1/E3-deleted replication-deficient adenovirus (CTL102) encoding the bacterial nitroreductase enzyme in combination with prodrug CB1954. This study has provided an opportunity to monitor and characterize vector- and tumor-specific adaptive immunity before and after single or repeat injections of adenovirus. Here we report robust vector-specific humoral and cellular immune responses in all patients monitored. However, we found no correlation between preexisting immunity or the magnitude of the immune response to vector and the clinical outcome as measured by changes in serum prostate-specific antigen (PSA) level. Increased frequency of T cells recognizing prostate-specific antigens PSA or prostate-specific membrane antigen (PSMA) was detected in 3 of 11 patients after therapy, suggesting that this direct cytotoxic strategy can also stimulate tumor-specific immunity.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Cancer Research Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Human Gene Therapy | ||||
Publisher: | Mary Ann Liebert, Inc. Publishers | ||||
ISSN: | 1043-0342 | ||||
Official Date: | 2009 | ||||
Dates: |
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Volume: | 20 | ||||
Number: | 11 | ||||
Page Range: | pp. 1249-1258 | ||||
DOI: | 10.1089/hum.2009.078 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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