DNA vaccines, electroporation and their applications in cancer treatment

Lee, Si-Hyeong; Danishmalik, Sayyed Nilofar; Sin, Jeong-Im

doi:10.1080/21645515.2015.1035502

Cited by 67 publications

(51 citation statements)

References 144 publications

(92 reference statements)

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“…DNA vaccines have received increasing attention due to their ability to induce both humoral and cellular immune responses. DNA vaccines can induce a strong CTL reaction in the treatment of cancer and chronic infectious diseases, and they have an advantage over other types of vaccines due to their strong CTL reactions [2]. DNA vaccines are made up of eukaryotic expression plasmids that carry an antigen of interest.…”

Section: Introductionmentioning

confidence: 99%

The immunogenicity and anti-tumor effects of a lung cancer DNA vaccine harboring a MUC-1 and GM-CSF fusion gene

Yang

Jiang

Zhu

et al. 2016

Braz. arch. biol. technol.

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Section: Introductionmentioning

confidence: 99%

The immunogenicity and anti-tumor effects of a lung cancer DNA vaccine harboring a MUC-1 and GM-CSF fusion gene

Yang

Jiang

Zhu

et al. 2016

Braz. arch. biol. technol.

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“…Hence, several efforts have been made to improve the potency of DNA vectors. These efforts include increasing the transfection frequency in vivo 13,14 most notably using DNA electroporation (EP). 15 The EP procedure itself induces inflammation while being safe and tolerable.…”

Section: Introductionmentioning

confidence: 99%

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

Wall

Ljungberg

et al. 2018

OncoImmunology

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Cervical cancer develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7. Our group pioneered a recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. The most striking benefit of this alphavirus vector-based vaccine platform is its high potency. DNA vaccines on the other hand, have a major advantage with respect to ease of production. In this study, the benefits associated with both SFV-based vaccines and DNA vaccines were combined with the development of a DNA-launched RNA replicon (DREP) vaccine targeting cervical cancer. Using intradermal delivery followed by electroporation, we demonstrated that DREP encoding for E6,7 (DREP-E6,7) induced effective, therapeutic antitumor immunity. While immunizations with a conventional DNA vaccine did not prevent tumor outgrowth, immunization with a 200-fold lower equimolar dose of DREP (0.05 µg of DREP) resulted in approximately 85% of tumor-free mice. To overcome the safety concern of potential malignant transformation at the vaccination site, we evaluated the anti-tumor effect of a DREP vaccine encoding a shuffled version of E7 (DREP-E7sh). DREP-E7sh delayed tumor growth yet not to the same extent as DREP-E6,7. In addition, inclusion of a helper cassette and an ER targeting signal (sigHelp) did not significantly further enhance the suppression of tumor outgrowth in the long term, albeit exhibiting better tumor control early after immunization. Collectively, this study points towards the clinical evaluation of DREP encoding HPV antigens as a potent immunotherapy for patients with HPV16 (pre)-malignancies.

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“…3,4) The use of bacteria as a delivery vehicle for DNA vaccines has emerged recently as a promising approach to enhance potency, 5) and one of the attractive features of the use of bacteria is the potential for oral administration to induce not only systemic but also mucosal immune responses. 5) Salmonella typhimurium and Listeria monocytogenes (L. monocytogenes) have been studied as experimental delivery vehicles as they are known to invade intestinal epithelial cells.…”

Section: )mentioning

confidence: 99%

Peyer’s Patches as a Portal for DNA Delivery by <i>Lactococcus lactis</i> <i>in Vivo</i>

Yano

Takahashi

Mori

et al. 2018

Biological & Pharmaceutical Bulletin

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Application of food-grade Lactococcus lactis (L. lactis) as a safe delivery tool for DNA vaccines and therapeutic proteins has been well investigated. Although some studies showed that eukaryotic expression plasmids were transferred from L. lactis to enterocytes, the precise mechanism of the DNA transfer remains unknown. In this study, we generated an invasive L. lactis strain that expresses "murinized" Internalin A, an invasin of intracellular bacteria Listeria monocytogenes with two amino acid alterations for invasion into murine cells, and confirmed that this L. lactis strain delivered DNA in an invasin-dependent manner into a monolayer of epithelial cells polarized to mimic the gastrointestinal tract environment. Although invasive L. lactis inoculated orally can deliver DNA into enterocytes in the gastrointestinal tract of mice, the efficiency of DNA transfer was similar to that of non-invasive L. lactis strain, suggesting that the in vivo DNA transfer from L. lactis occurs invasin-independently. A ligated-intestinal loop assay, a method for a short-term culturing of the whole intestine filled with materials to evaluate the interaction of the materials with intestinal cells, demonstrated that both non-invasive and invasive L. lactis strains were present in the Peyer's patches of the small intestine. On the other hand, few L. lactis was detected in the non-Peyer's patch epithelial region. Thus, our observations lead us to speculate that DNA transfer from L. lactis occurs predominantly in the Peyer's patches in an invasin-independent manner. Key words Lactococcus lactis;Peyer's patch; DNA delivery; Internalin A Vaccination with a plasmid containing the DNA sequence encoding an antigen has been of great interest of late as it can induce both humoral and cell-mediated immune responses. 1)Despite numerous studies, no DNA vaccines have been licensed for human use to date. The administration of naked DNA is less immunogenic in large animals and humans, probably due to the low level of protein expression.2) To improve the potency of DNA vaccination, various DNA delivery platforms, including electroporation, needle-free jet injection and liposomes, have been developed. 3,4) The use of bacteria as a delivery vehicle for DNA vaccines has emerged recently as a promising approach to enhance potency, 5) and one of the attractive features of the use of bacteria is the potential for oral administration to induce not only systemic but also mucosal immune responses. 5) Salmonella typhimurium and Listeria monocytogenes (L. monocytogenes) have been studied as experimental delivery vehicles as they are known to invade intestinal epithelial cells. 6) Even though the strains employed are extensively attenuated for virulence, the possibility of reversion to virulence as well as preexisting immunity limits their clinical use, especially for infants, the elderly and immunocompromised hosts. 7,8) The mechanisms involving DNA transfer from bacteria to mammalian cells and tissues remain to be clarified.The use of food-grade Lactococcus ...

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DNA vaccines, electroporation and their applications in cancer treatment

Cited by 67 publications

References 144 publications

The immunogenicity and anti-tumor effects of a lung cancer DNA vaccine harboring a MUC-1 and GM-CSF fusion gene

The immunogenicity and anti-tumor effects of a lung cancer DNA vaccine harboring a MUC-1 and GM-CSF fusion gene

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

Peyer’s Patches as a Portal for DNA Delivery by <i>Lactococcus lactis</i> <i>in Vivo</i>

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