DNA Vaccines for Prostate Cancer

McNeel, Douglas G.; Becker, Jordan T.; Johnson, Laura E.; Olson, Brian M.

doi:10.2174/157339412804143113

Cited by 9 publications

(9 citation statements)

References 32 publications

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“…DNA-based vaccines have shown to produce antigen-specific humoral- and cellular-immune responses in several organisms [ 17 – 19 ]. They are safe as they are non-live, non-spreading and non-replicating [ 12 , 20 – 22 ]. As it is the host that is producing the antigenic protein of interest [ 19 , 23 ], the antigens will have those post-translational modifications produced during a real infection [ 19 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

et al. 2015

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BackgroundThe current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.MethodsWe analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.ResultsThe proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.ConclusionThese results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

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Section: Introductionmentioning

confidence: 99%

Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

et al. 2015

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“…In this trial delayed-type I hypersensitivity responses were observed [ 38 ]. Therefore, subsequent trials pursued the goal to improve this parameter [ 39 ]. Vaccination of melanoma patients with a bivalent DNA encoding Melan-A and tyrosinase as tumor-associated antigens elicited humoral and CTL responses in Stage IV patients [ 40 ].…”

Section: Dna Vaccines In the Clinicmentioning

confidence: 99%

DNA Vaccines—How Far From Clinical Use?

Hobernik

Bros

2018

IJMS

356

332

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Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses. Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies. This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far. Important optimization steps that improve DNA transfection efficiency comprise the introduction of DNA-complexing nano-carriers aimed to prevent extracellular DNA degradation, enabling APC targeting, and enhanced endo/lysosomal escape of DNA. Attachment of virus-derived nuclear localization sequences facilitates nuclear entry of DNA. Improvements in DNA vaccine design include the use of APC-specific promotors for transcriptional targeting, the arrangement of multiple antigen sequences, the co-delivery of molecular adjuvants to prevent tolerance induction, and strategies to circumvent potential inhibitory effects of the vector backbone. Successful clinical use of DNA vaccines may require combined employment of all of these parameters, and combination treatment with additional drugs.

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“…We have previously reviewed clinical trials using DNA vaccines as treatments for prostate cancer (McNeel et al, 2012). These completed and ongoing clinical trials are summarized in Table 1.…”

Section: Clinical Trials With Dna Vaccines For Prostate Cancermentioning

confidence: 99%

DNA vaccines for prostate cancer

Zahm

Colluru

McNeel

2017

Pharmacology & Therapeutics

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DNA vaccines offer many advantages over other anti-tumor vaccine approaches due to their simplicity, ease of manufacturing, and safety. Results from several clinical trials in patients with cancer have demonstrated that DNA vaccines are safe and can elicit immune responses. However, to date few DNA vaccines have progressed beyond phase I clinical trial evaluation. Studies into the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to directly present or cross-present DNA-encoded antigens, and the activation of innate immune responses due to DNA itself, have suggested opportunities to increase the immunogenicity of these vaccines. In addition, studies into the mechanisms of tumor resistance to anti-tumor vaccination have suggested combination approaches that can increase the antitumor effect of DNA vaccines. This review focuses on these mechanisms of action and mechanisms of resistance using DNA vaccines, and how this information is being used to improve the anti-tumor effect of DNA vaccines. These approaches are then specifically discussed in the context of human prostate cancer, a disease for which DNA vaccines have been and continue to be explored as treatments.

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DNA Vaccines for Prostate Cancer

Cited by 9 publications

References 32 publications

Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

DNA Vaccines—How Far From Clinical Use?

DNA vaccines for prostate cancer

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