1995

DOI: 10.1016/1074-7613(95)90085-3

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Exposing the immunology of naked DNA vaccines

Drew M. Pardoll

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Anne Marie Beckerleg

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Cited by 242 publications

(103 citation statements)

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“…They are then translated into functional proteins, processed into peptides and presented by major histocompatibility (MHC) molecules to immune T cells. 2 Direct DNA transfer has been successfully used for in vitro induction of both humoral and cellular immune responses to several antigens, including viruses such as influenza, hepatitis B, or HIV (human immunodeficiency virus), parasites, or tumor antigens. [3][4][5][6][7][8] Additionally, systemic effects were observed after transfer of cytokine genes.…”

Section: Introductionmentioning

confidence: 99%

Superiority of the ear pinna over muscle tissue as site for DNA vaccination

¹

,

²

,

et al. 1998

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Three different vaccination sites were compared for expression vector used. The cytomegalus virus promoter efficiency of immunization with naked DNA. Using the bacdriven pCMV␤ vector was superior to the Moloney murine terial lacZ gene as a model, all three sites of the mouse leukemia virus LTR driven BAG vector. LacZ DNA immuni-(skeletal muscle, dermis of abdominal skin or of the ear zation was also compared with cell-based vaccination with pinna) could express the gene product ␤-gal but varied in lacZ-transfected tumor cells, in which case again the pinna expression time with muscle tissue showing the longest was the best site for inducing strong immune responses. expression. Expression time, however, did not correlateTumor-specific T cell responses could also be well induced with immune response intensity. The ear pinna was by far in the pinna, leading to cytotoxic T lymphocyte induction the most effective and muscle the least effective priming and protective antitumor immunity. Thus, the pinna was site for specific humoral and cytotoxic T cell-mediated found to be a privileged site for induction of antitumor immune responses. Following intra-pinna DNA inoculation, responses and for genetic immunization, an important find-␤-gal expressing cells were detectable around the injection ing of immediate practical and potential future clinical site and in the major draining lymph node. Efficiency of implications. immunization was also dependent on the promoter and

“…They are then translated into functional proteins, processed into peptides and presented by major histocompatibility (MHC) molecules to immune T cells. 2 Direct DNA transfer has been successfully used for in vitro induction of both humoral and cellular immune responses to several antigens, including viruses such as influenza, hepatitis B, or HIV (human immunodeficiency virus), parasites, or tumor antigens. [3][4][5][6][7][8] Additionally, systemic effects were observed after transfer of cytokine genes.…”

Section: Introductionmentioning

confidence: 99%

Superiority of the ear pinna over muscle tissue as site for DNA vaccination

¹

,

²

,

et al. 1998

View full text Add to dashboard Cite

Three different vaccination sites were compared for expression vector used. The cytomegalus virus promoter efficiency of immunization with naked DNA. Using the bacdriven pCMV␤ vector was superior to the Moloney murine terial lacZ gene as a model, all three sites of the mouse leukemia virus LTR driven BAG vector. LacZ DNA immuni-(skeletal muscle, dermis of abdominal skin or of the ear zation was also compared with cell-based vaccination with pinna) could express the gene product ␤-gal but varied in lacZ-transfected tumor cells, in which case again the pinna expression time with muscle tissue showing the longest was the best site for inducing strong immune responses. expression. Expression time, however, did not correlateTumor-specific T cell responses could also be well induced with immune response intensity. The ear pinna was by far in the pinna, leading to cytotoxic T lymphocyte induction the most effective and muscle the least effective priming and protective antitumor immunity. Thus, the pinna was site for specific humoral and cytotoxic T cell-mediated found to be a privileged site for induction of antitumor immune responses. Following intra-pinna DNA inoculation, responses and for genetic immunization, an important find-␤-gal expressing cells were detectable around the injection ing of immediate practical and potential future clinical site and in the major draining lymph node. Efficiency of implications. immunization was also dependent on the promoter and

“…33,47,48 Therefore, increasing the inherent immunogenicity of plasmid DNA by complexing to cationic liposomes would be expected to increase potentially the overall effectiveness of a DNA vaccine. Therefore, we reasoned that LDC might serve as a more efficient means of delivering DNA vaccines for cancer.…”

Section: Discussionmentioning

confidence: 99%

“…29,31 However, in human clinical trials, plasmid DNA vaccines have generally failed to elicit significant antitumor activity in patients with established tumors. 8,32,33 Thus, despite the theoretical advantages of plasmid DNA vaccination, there are still significant unresolved issues in the application of plasmid DNA vaccination for therapeutic induction of antitumor immunity.…”

Section: Introductionmentioning

confidence: 99%

Vaccination with liposome–DNA complexes elicits enhanced antitumor immunity

¹

,

²

,

³

2006

Cancer Gene Ther

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Cationic liposomes have been shown to potentiate markedly the ability of plasmid DNA to activate innate immune responses. We reasoned therefore that liposome-DNA complexes (LDC) could be used to produce more effective plasmid DNA vaccines for cancer. To test this hypothesis, tumor-bearing mice were vaccinated with conventional plasmid DNA vaccines or with LDC vaccines encoding model tumor antigens and CD8 þ T-cell responses and antitumor activity were assessed. We found that although plasmid DNA vaccines generated large increases in antigen-specific CD8 þ T cells, they failed to elicit significant antitumor immunity. In contrast, LDC vaccines elicited large numbers of antigen-specific CD8 þ T cells and also generated significant antitumor activity against established tumors. The antitumor activity elicited by immunization with LDC vaccines was mediated primarily by CD8 þ T cells. Studies of the interaction of LDC with antigen-presenting cells found that LDC triggered dendritic cell production of interleukin-12 and interferon (IFN)-g production by natural killer cells in vivo. Activation by LDC was also accompanied by upregulation of costimulatory molecule expression. These findings suggest that by concurrently activating strong systemic innate immune responses and generating cytotoxic T-lymphocyte responses, LDC may be used to increase the effectiveness of therapeutic plasmid DNA vaccination for cancer.

“…One novel and powerful strategy for anti-tumor vaccination developed in our laboratory is the epicutaneous application of an adenovirus vector encoding tumor-associated antigens such as the human carcinoembryonic antigen (CPA) [3]. This technique utilizes DNA immunization which is known to induce both antigen-specific cellular as well as humoral immune responses [4,5]. The generation of T cell-mediated cytotoxicity or antibody-mediated cytotoxicity against tumor cells can inhibit tumor growth and lead to tumorrejection [1].…”

Section: Introductionmentioning

confidence: 99%

A differential proteome in tumors suppressed by an adenovirus‐based skin patch vaccine encoding human carcinoembryonic antigen

Shi²,

et al. 2005

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We created an anti-tumor vaccine by using adenovirus as a vector which contains a cytomegalovirus early promoter-directed human carcinoembryonic antigen gene (AdCMVhCEA). In an attempt to develop the skin patch vaccine, we epicutaneously vaccinated Balb/c mice with AdCMV-hCPA. After nine weeks post-immunization, vaccinated mice evoked a robust antibody titer to CEA and demonstrated the capability of suppressing in vivo growth of implanted murine mammay adenocarioma cell line (JC-hCEA) tumor cells derived from a female Balb/c mouse. Proteomic analysis of the tumor masses in the non-vaccinated naïve and vaccinated mice reveal that six proteins change their abundance in the tumor mass. The levels of adenylate kinase 1, β-enolase, creatine kinase M chain, hemoglobin beta chain and prohibitin were statistically increased whereas the level of a creatine kinase fragment, which is undocumented, was decreased in the tumor of vaccinated mice. These proteins may provide a vital link between early-stage tumor suppression and immune response of skin patch vaccination.

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