Prostate Stem Cell Antigen DNA Vaccination Breaks Tolerance to Self-antigen and Inhibits Prostate Cancer Growth

Ahmad, Sarfraz; Casey, Garrett; Sweeney, Paul; Tangney, Mark; O’Sullivan, Gerald C.

doi:10.1038/mt.2009.66

Cited by 39 publications

(42 citation statements)

References 42 publications

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“…Vaccination strategies involving bactofection of antigen presenting cells (APC) with defined tumor antigen genes using replication deficient mutants of Salmonella enterica Typhimurium and Listeria monocytogenes have shown significant promise both preclinically and in clinical trials. 6,7 After oral intake, such bacterial vector cells are phagocytosed by monocytes in the intestine, which differentiate and migrate to lymph nodes and the spleen. Subsequently, the attenuated strains (unable to replicate in hosts) lyse and release plasmid into the cytoplasm of monocytes, followed by expression of the desired antigen and presentation to the immune system.…”

Section: Introductionmentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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The significant burden of resistance to conventional anticancer treatments in patients with advanced disease has prompted the need to explore alternative therapeutic strategies. The challenge for oncology researchers is to identify a therapy which is selective for tumors with limited toxicity to normal tissue. Engineered bacteria have the unique potential to overcome traditional therapies' limitations by specifically targeting tumors. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally, either external to (non-invasive species) or within tumor cells (pathogens). Pre-clinical and clinical investigations involving bacterial vectors require relevant means of monitoring vector trafficking and levels over time, and development of bacterial-specific real-time imaging modalities are key for successful development of clinical bacterial gene delivery. This review discusses the currently available imaging technologies and the progress to date exploiting these for monitoring of bacterial gene delivery in vivo.Cancer Gene Therapy ( INTRODUCTIONAlthough the potential anti-cancer effects of acquired bacterial infection have been evident for over 120 years and the presence of bacteria in excised tumors has been noted for over 60 years, 1 it is only in more recent times that the tumor-specific growth of bacteria has been considered for therapeutic purposes. While the precise mechanism(s) behind preferential bacterial tumor colonization remain poorly understood, this phenomenon must relate to unique tumor attributes that separate them from healthy tissues. Factors such as the irregular blood supply; local immune suppression; inflammation; and unique nutrient supply (e.g., purines) in tumors have been proposed to play a role. 2 Bacterial entry into the tumor environment is proposed to be facilitated by the leaky vasculature. Cancer cells are characterized by an aberrantly accelerated metabolism and proliferation leading to an imbalance of oxygen supply and consumption which is a major causative factor of tumor hypoxia. 3 The hypoxic nature of solid tumors enhances the growth of anaerobic and facultatively anaerobic bacteria. In addition, these areas with low oxygen and high interstitial pressure are considered to be an immunological sanctuary, where bacterial clearance mechanisms are greatly inhibited. 4 Necrotic regions are also rich in nutrients favoured by bacteria due to tumor cell turnover. However, tumor selective bacterial colonization now appears to be both bacterial species and tumor origin independent, since aerobic bacteria are also capable of colonising tumors, and even small tumors lacking an anaerobic center are colonised. See Figure 1 for proposed mechanisms.Invasive bacteria can internalize and replicate within tumor cells, while non-invasive bacteria grow externally to tumor cells, within the tumor micro-environment. 5 The tumor selective growth of bacteria has made them an attractive vehicle for the delivery of ...

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Section: Introductionmentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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“…Human PSCA is overexpressed in ~90% of primary or metastatic prostate cancers with higher levels associated with higher tumor grade and stage [32]. A murine PSCA homologue exists, 65% homologous to the human protein, and is known to be expressed in prostate tumor cells in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model, thus providing a relevant preclinical model to investigate vaccines encoding PSCA [33, 34]. Similarly, STEAP is also expressed in normal prostate tissues but is overexpressed in human prostate cancer tissue.…”

Section: Introduction: Cancer Immunotherapy and Anti-tumor Vaccinesmentioning

confidence: 99%

“…Other groups have also evaluated PSCA as a target using DNA vaccines using approaches to increase antigen presentation at the time of immunization [34, 37]. In particular, Zhang and colleagues have evaluated DNA vaccines encoding PSCA with or without HSP70.…”

Section: Introduction: Cancer Immunotherapy and Anti-tumor Vaccinesmentioning

confidence: 99%

“…These studies identified that intradermal DNA electroporation resulted in rapid and stable transgene expression, and led to the generation of PSA-specific CD8 + T cells. In another study described earlier, a DNA vaccine encoding mPSCA was delivered intramuscularly by electroporation to C57/B16 mice and then mice were challenged with TRAMP-C1 cells [34]. mPSCA vaccinated mice demonstrated inhibition of tumor growth or and greater survival relative to control vaccinated mice, however the specific enhancement provided by electroporation was not investigated [34].…”

Section: Introduction: Cancer Immunotherapy and Anti-tumor Vaccinesmentioning

confidence: 99%

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DNA Vaccines for Prostate Cancer

McNeel

Becker

Johnson

et al. 2012

Current Cancer Therapy Reviews

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Delivery of plasmid DNA encoding an antigen of interest has been demonstrated to be an effective means of immunization, capable of eliciting antigen-specific T cells. Plasmid DNA vaccines offer advantages over other anti-tumor vaccine approaches in terms of simplicity, manufacturing, and possibly safety. The primary disadvantage is their poor transfection efficiency and subsequent lower immunogenicity relative to other genetic vaccine approaches. However, multiple preclinical models demonstrate anti-tumor efficacy, and many efforts are underway to improve the immunogenicity and anti-tumor effect of these vaccines. Clinical trials using DNA vaccines as treatments for prostate cancer have begun, and to date have demonstrated safety and immunological effect. This review will focus on DNA vaccines as a specific means of antigen delivery, advantages and disadvantages of this type of immunization, previous experience in preclinical models and human trials specifically conducted for the treatment of prostate cancer, and future directions for the application of DNA vaccines to prostate cancer immunotherapy.

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“…One of the methods that improve DNA penetration of the cell is electroporation [Lee et al, 2009;, Harrison et al, 1998;Rossini et al, 2002;Ahmad et al, 2009;Collins et al, 2006;Kang et al, 2011;]. In vivo use of electroporation is done by injecting naked DNA followed by electric pulses from electrodes that are located in situ in the target tissues.…”

Section: Electroporationmentioning

confidence: 99%