DNA vaccination for prostate cancer: key concepts and considerations.

Grace Cole,Ahlam A Ali,Helen O Mccarthy,Joanne Mccaffrey

doi:10.1186/s12645-015-0010-5

Abstract

While locally confined prostate cancer is associated with a low five year mortality rate, advanced or metastatic disease remains a major challenge for healthcare professionals to treat and is usually terminal. As such, there is a need for the development of new, efficacious therapies for prostate cancer. Immunotherapy represents a promising approach where the host’s immune system is harnessed to mount an anti-tumour effect, and the licensing of the first prostate cancer specific immunotherapy in 2010 has opened the door for other immunotherapies to gain regulatory approval. Among these strategies DNA vaccines are an attractive option in terms of their ability to elicit a highly specific, potent and wide-sweeping immune response. Several DNA vaccines have been tested for prostate cancer and while they have demonstrated a good safety profile they have faced problems with low efficacy and immunogenicity compared to other immunotherapeutic approaches. This review focuses on the positive aspects of DNA vaccines for prostate cancer that have been assessed in preclinical and clinical trials thus far and examines the key considerations that must be employed to improve the efficacy and immunogenicity of these vaccines.

Highlights

Prostate cancer represents a major challenge to healthcare and accounts for 25 % of all new diagnoses in males in the UK annually [1]
Conclusions and future considerations Physical delivery systems use the application of force to overcome the extra- and intracellular barriers to gene delivery
Non-physical delivery methods carry the advantage of enhancing gene delivery in a non-invasive means to patients without requiring specialist equipment

Summary

Introduction

Prostate cancer represents a major challenge to healthcare and accounts for 25 % of all new diagnoses in males in the UK annually [1]. There is a trade-off between increased efficacy and discomfort to the patient, with the latter being the rate-limiting factor [42] Despite these concerns EP has been used safely in a number of key prostate cancer clinical trials [47, 48], providing an encouraging platform for DNA vaccine delivery. Its use as a delivery agent in clinical trials for cancer treatment has been less successful, perhaps due to limited gene carrying capacity (~2 μg per dose), which often necessitates multiple immunisations at different sites in the body, reducing patient compliance [52,53,54] Despite this dose limitation the gene gun is a simple and flexible device for in vivo gene delivery and has been used for the delivery of prostate TAAs in several preclinical studies. EP and the gene gun have been used for DNA vaccination in numerous clinical trials and have well established safety profiles, ultrasound has not been evaluated to the same extent and the long term toxicity and efficacy still require elucidation

Conclusions and future considerations

Conclusions

Findings