DNA vaccination for prostate cancer, from preclinical to clinical trials - where we stand?

Sarfraz Ahmad,Gerald C Sullivan,Paul Sweeney,Mark Tangney

doi:10.1186/1479-0556-10-9

Sarfraz Ahmad, Gerald C Sullivan + Show 2 more

Open Access

https://doi.org/10.1186/1479-0556-10-9

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Abstract

Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa.

Highlights

Prostate cancer (PCa) is a major urological problem associated with significant morbidity and mortality [1]
This study provided 12 months follow up data and demonstrated that the DNA vaccine is safe, elicits an antigen-specific T-cell response, and may be associated with an increased prostate specific antigen (PSA) doubling time
Conclusions and future directions DNA vaccination for PCa is at a crucial developmental stage

Summary

Introduction

Prostate cancer (PCa) is a major urological problem associated with significant morbidity and mortality [1]. Mincheff et al [53] evaluated two plasmid DNA vaccines, encoding either PSMA products that are retained in the cytosol and degraded in the proteasome (tVacs; hPSMAt), or secreted proteins (sVacs; hPSMAs) for stimulation of cytotoxic cell or antibody responses. They observed that immunisation with both vectors led to generation of cell cytotoxicity, provided GM-CSF was administered with the vaccine. GMCSF and IL-2, were used as vaccine adjuvants The results of this trial demonstrated that DNA vaccination with a PSA-coding plasmid vector, given with GM-CSF and IL-2, is safe and can induce cellular and humoural immune responses against PSA. Three vaccinations were given at 0, 4, and 8 weeks, with

Conclusions and future directions

Findings

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