Table of Contents
To view the fulltext, log-in or choose pay-per-view options:
Get Access

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

Mincheff M.a,c · Tchakarov S.b · Zoubak S.a · Loukinov D.a · Botev C.c · Altankova I.d · Georgiev G.d · Petrov S.b · Meryman H.T.a
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 Eur Urol 2000;38:208–217 (DOI:10.1159/000020281)

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.

 

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50