Co-transfection Gene Delivery of Dendritic Cells Induced Effective Lymph Node Targeting and Anti-tumor Vaccination

Chen, Yu-Zhe; Ruan, Gui‐Xin; Yao, Xinglei; Li, Liming; Hu, Ying; Tabata, Yasuhiko

doi:10.1007/s11095-013-0985-8

Cited by 25 publications

(25 citation statements)

References 46 publications

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“…[5][6][7] Dendritic cells have been demonstrated At the designated times post injection, Tc-99m (300 μCi; 11.1 MBq) was administered to mice under general anesthesia by i.p. injection of 0.3 mL of a 1:1:9 RKS solution.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] Specifically, tumor cell death is achieved by introducing a tumor specific DNA immunogen, which induces the production of Type 1 T helper cell (Th1) cytokines (such as tumor necrosis factor) and the resulting expansion of tumor-specific CTLs. [1][2][3][4] The ability to monitor the in vivo kinetics of expression of the injected tumor genes is crucial for mechanistic studies of DNA-based vaccines, and several groups [5][6][7][8] are currently working to achieve efficient in vivo DNA transfection using a number of different vectors. To date, the methods used to determine the efficacy of DNA vaccines have relied on evidence of T-cell−mediated immune responses.…”

Section: Introductionmentioning

confidence: 99%

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In vivo monitoring of transfected DNA, gene expression kinetics, and cellular immune responses in mice immunized with a human NIS gene-expressing plasmid

Son

Jeon

Chung

et al. 2016

Int J Immunopathol Pharmacol

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In assessing the effectiveness of DNA vaccines, it is important to monitor: (1) the kinetics of target gene expression in vivo; and (2) the movement of cells that become transfected with the plasmid DNA used in the immunization of a subject. In this study, we used, as a visual imaging marker, expression of the transfected human sodium/iodide symporter (hNIS) gene, which enhances intracellular radio-pertechnetate (TcO4-) accumulation. After intradermal (i.d.) and systemic injection of mice with pcDNA-hNIS and radioactive Technetium-99m (Tc-99m), respectively, whole-body images were obtained by nuclear scintigraphy. The migration of mice cells transfected with the hNIS gene was monitored over a 2-week period by gamma-radioactivity counting of isolated cell populations and was demonstrated in peripheral lymphoid tissues, especially in the draining lymph nodes (dLNs). Beginning at 24 h after DNA inoculation and continuing for the 2-week monitoring period, hNIS-expressing cells were observed specifically in the T-cell-rich zones of the paracortical area of the dLNs. Over the same time period, high levels of INF-γ-secreting CD8 T-cells were found in the dLNs of the pcDNA-hNIS immunized mice. Tumor growth was also significantly retarded in the mice that received hNIS DNA immunization followed by inoculation with CT26 colorectal adenocarcinoma cells that had been transfected with the rat NIS gene (rNIS), which is 93% homologous to the hNIS gene. In conclusion, mouse cells transfected with hNIS DNA after i.d. immunization were found to traffic to the dLNs, and hNIS gene expression in these cells continued for at least 2 weeks post immunization. Furthermore, sequential presentation of NIS DNA to T-cells by migratory antigen presenting cells could induce NIS DNA-specific Th1 immune responses and thus retard the growth of NIS-expressing tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo monitoring of transfected DNA, gene expression kinetics, and cellular immune responses in mice immunized with a human NIS gene-expressing plasmid

Son

Jeon

Chung

et al. 2016

Int J Immunopathol Pharmacol

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“…Migration of tumor antigenpulsed DCs to lymph nodes is related to maturation state of DCs [67]. Expression of chemokine receptors such as CCR7 in mature DCs is important in the migration of DC into lymph nodes [68]. In addition, the route of DC vaccination and number of DCs reach the lymph nodes can affect therapeutic efficacy of DC vaccines.…”

Section: Obstacles In the Generation Of Effective Antitumor Immunity mentioning

confidence: 99%

Anticancer Dendritic Cell Vaccines Producing effective Antitumor T Cell Responses

Khansari¹

2017

IJVV

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In the past two decades, immunotherapy has been investigated as a novel modality in cancer therapy. The aim of immunotherapy is augmenting body's immune system to recognize and destroy malignant cells efficiently and safely. Dendritic cell (DC)-based vaccination is one of the most important approaches of cancer immunotherapy, in which autologous ex vivo generated tumor antigen-loaded DCs are injected to cancer patients in order to augment antitumor immunity. Various DC culture conditions, tumor antigen sources, antigen loading strategies, DC maturation stimuli, and routes of vaccination have been used to increase efficacy of DC vaccines. However, therapeutic efficacy of DC vaccines is still limited in cancer patients and preparation of clinical-grade DCs should be standardized to generate immuno stimulatory DCs and to prevent development of immunosuppressive DCs. Understanding DC function in triggering adaptive immunity or induction of immunological tolerance in cancer setting may be helpful in improving therapeutic efficacy of DC vaccines. In this article, we reviewed DCs interactions with T cells, efficacy of ex vivo generated DCs in triggering/suppression of antitumor effector T cell responses, as well as recent findings about DC vaccinations in cancer patients.

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“…Such vectors have low adverse immunologic effects in contrast to viral ones when applied in vivo. Non-viral vectors are widely used for delivery of nucleic acids into DCs and provide effective anticancer immune responses [25][26][27][28][29]. Furthermore, several chemical vectors such as cationic liposomes play also a role of maturation signal for DCs [30,31].…”

Section: Introductionmentioning

confidence: 99%

Multicomponent mannose-containing liposomes efficiently deliver RNA in murine immature dendritic cells and provide productive anti-tumour response in murine melanoma model

Markov

Миронова

Shmendel

et al. 2015

Journal of Controlled Release

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Co-transfection Gene Delivery of Dendritic Cells Induced Effective Lymph Node Targeting and Anti-tumor Vaccination

Abstract: The study is the first to report the application of nonviral vector SD to co-transfect DC with gp100 and CCR7-coding plasmid to induce both the capacity of antigen presentation and lymph node targeting.

Cited by 25 publications

References 46 publications

In vivo monitoring of transfected DNA, gene expression kinetics, and cellular immune responses in mice immunized with a human NIS gene-expressing plasmid

In vivo monitoring of transfected DNA, gene expression kinetics, and cellular immune responses in mice immunized with a human NIS gene-expressing plasmid

Anticancer Dendritic Cell Vaccines Producing effective Antitumor T Cell Responses

Multicomponent mannose-containing liposomes efficiently deliver RNA in murine immature dendritic cells and provide productive anti-tumour response in murine melanoma model

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