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Vol. 38, No. 2, 2000
Issue release date: August 2000
Section title: Prostate Cancer
Eur Urol 2000;38:208–217
(DOI:10.1159/000020281)

Naked DNA and Adenoviral Immunizations for Immunotherapy of Prostate Cancer: A Phase I/II Clinical Trial

Mincheff M. · Tchakarov S. · Zoubak S. · Loukinov D. · Botev C. · Altankova I. · Georgiev G. · Petrov S. · Meryman H.T.
aAmerican Foundation for Biological Research, Rockville, Md., USA, bSt. Ann Faculty Hospital, cNational Center for Hematology and Transfusion Medicine, and dSt. Ivan Rilski Hospital, Sofia, Bulgaria

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Article / Publication Details

First-Page Preview
Abstract of Prostate Cancer

Published online: 7/5/2000

Number of Print Pages: 10
Number of Figures: 7
Number of Tables: 1

ISSN: 0302-2838 (Print)
eISSN: 1421-993X (Online)

For additional information: http://www.karger.com/EUR

Abstract

Introduction and Objectives: Animal studies have indicated that the use of syngeneic dendritic cells that have been transfected ex vivo with DNA for tumor–specific antigen results in tumor regression and decreased number of metastases. Additional studies have also suggested the possibility to modulate the dendritic cells in vivo either by ‘naked’ DNA immunization or by injecting replication–deficient viral vectors that carry the tumor–specific DNA. Using the prostate– specific membrane antigen (PSMA) as a target molecule, we have initiated a clinical trial for immunotherapy of prostate cancer. The primary objective of the study was to determine the safety of the PSMA vaccine after repeated intradermal injections.

Methods: We have included the extracellular human PSMA DNA as well as the human CD86 DNA into separate expression vectors (PSMA and CD86 plasmids), and into a combined PSMA/CD86 plasmid. In addition, the expression cassette from the PSMA plasmid was inserted into a replication deficient adenoviral expression vector. Twenty–six patients with prostate cancer were entered into a phase I/II toxicity–dose escalation study, which was initiated in spring 1998. Immunizations were performed intradermally at weekly intervals. Doses of DNA between 100 and 800 μg and of recombinant virus at 5×108 PFUs per application were used.

Results and Conclusion: No immediate or long–term side effects following immunizations have been recorded. All patients who received initial inoculation with the viral vector followed by PSMA plasmid boosts showed signs of immunization as evidenced by the development of a delayed–type hypersensitivity reaction after the PSMA plasmid injection. In contrast, of the patients who received a PSMA plasmid and CD86 plasmid, only 50% showed signs of successful immunization. Of the patients who received PSMA plasmid and soluble GM–CSF, 67% were immunized. However, all patients who received the PSMA/CD86 plasmid and sGM–CSF became immunized. The patients who did not immunize during the first round were later successfully immunized after a boost with the viral vector. The heterogeneity of the medical status and the presence in many patients of concomitant hormone therapy does not permit unequivocal interpretation of the data with respect to the effectiveness of the therapy. However, several responders, as evidenced by a change in the local disease, distant metastases, and PSA levels, can be identified. A phase II clinical study to evaluate the effectiveness of the therapy is currently underway.


  

Author Contacts

Milcho Mincheff, MD, PhD
Biomedical Research Institute
12111 Parklawn Drive, Rockville, MD 20852 (USA)
Tel. +1 301 881 3300, ext. 124, Fax +1 301 881 7640
E–Mail mincheffm@netscape.net

  

Article Information

Accepted after revision: October 19, 1999
Number of Print Pages : 10
Number of Figures : 7, Number of Tables : 1, Number of References : 72

  

Publication Details

European Urology
Official Organ of the European Association of Urology

Vol. 38, No. 2, Year 2000 (Cover Date: August 2000)

Journal Editor: C.C. Schulman, Brussels
ISSN: 0302–2838 (print), 1421–993X (Online)

For additional information: http://www.karger.ch/journals/eur


Article / Publication Details

First-Page Preview
Abstract of Prostate Cancer

Published online: 7/5/2000

Number of Print Pages: 10
Number of Figures: 7
Number of Tables: 1

ISSN: 0302-2838 (Print)
eISSN: 1421-993X (Online)

For additional information: http://www.karger.com/EUR


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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