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A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer.

Abstract：

:Prostate-specific antigen (PSA) is a serine protease secreted at low levels by normal luminal epithelial cells of the prostate and in significantly higher levels by prostate cancer cells. Therefore, PSA is a potential target for various immunotherapeutical approaches against prostate cancer. DNA vaccination has been investigated as immunotherapy for infectious diseases in patients and for specific treatment of cancer in certain animal models. In animal studies, we have demonstrated that vaccination with plasmid vector pVAX/PSA results in PSA-specific cellular response and protection against tumour challenge. The purpose of the trial was to evaluate the safety, feasibility and biological efficacy of pVAX/PSA vaccine in the clinic. A phase I trial of pVAX/PSA, together with cytokine granulocyte/macrophage-colony stimulating factor (GM-CSF) (Molgramostim) and IL-2 (Aldesleukin) as vaccine adjuvants, was carried out in patients with hormone-refractory prostate cancer. To evaluate the biologically active dose, the vaccine was administered during five cycles in doses of 100, 300 and 900 microg, with three patients in each cohort. Eight patients were evaluable. A PSA-specific cellular immune response, measured by IFN-gamma production against recombinant PSA protein, and a rise in anti-PSA IgG were detected in two of three patients after vaccination in the highest dose cohort. A decrease in the slope of PSA was observed in the two patients exhibiting IFN-gamma production to PSA. No adverse effects (WHO grade >2) were observed in any dose cohort. We demonstrate that DNA vaccination with a PSA-coding plasmid vector, given with GM-CSF and IL-2 to patients with prostate cancer, is safe and in doses of 900 microg the vaccine can induce cellular and humoral immune responses against PSA protein.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Pavlenko M,Roos AK,Lundqvist A,Palmborg A,Miller AM,Ozenci V,Bergman B,Egevad L,Hellström M,Kiessling R,Masucci G,Wersäll P,Nilsson S,Pisa P

doi

10.1038/sj.bjc.6602019

subject

Has Abstract

pub_date

2004-08-16 00:00:00

pages

688-94

issue

eissn

0007-0920

issn

1532-1827

pii

6602019

journal_volume

pub_type

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A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer.