Addition of CpG ODN and Poly (I:C) to a standard maturation cocktail generates monocyte-derived dendritic cells and induces a potent Th1 polarization with migratory capacity

Zhu, Mei Ling; Wang, Xu; Su, Hong; Huang, Qiong; Wang, Baolong

doi:10.1080/21645515.2015.1046659

Cited by 14 publications

(8 citation statements)

References 64 publications

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“…For instance, Rizzo et al 28 reported that pretreatment with low-molecular-weight hyaluronan during the preparation of DC vaccines enhanced the migratory capacity of DCs through increasing the expression of CCR7. Zhu et al 29 showed that the addition of CpG ODN and Poly (I: C) to the maturation cocktail could generate DC vaccines with higher migratory potential. In the present study, our results showed that exposure to LDR during the preparation of DC vaccines also promoted the migration of DCs.…”

Section: Discussionmentioning

confidence: 99%

“…However, the production of IL-12 by a DC vaccine generated by conventional methods was still insufficient, which was considered to be responsible for, at least in part, the unsatisfying clinical outcomes of using DC vaccines for cancer immunotherapy. 29,38 Dendritic cell vaccines with an increased ability to produce IL-12 have been proven to prime stronger CTLs in vitro and result in greater tumor growth inhibition in vivo. 38,39 However, the authors did not report whether the administration of such a DC vaccine could result in a further increase in serum IL-12.…”

Section: Discussionmentioning

confidence: 99%

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Exposure to Low-Dose Radiation Enhanced the Antitumor Effect of a Dendritic Cell Vaccine

Wang¹,

Yu²,

He³

et al. 2019

Dose-Response

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The unsatisfactory clinical efficacy of dendritic cell (DC)-based cancer vaccines prepared by conventional methods is partly due to their insufficient capacity for migration. Our previous study showed that exposure to low-dose radiation (LDR) at a dose of 0.2 Gy promoted DC migration in vitro. The present study further investigates whether exposure to LDR at a dose of 0.2 Gy during the DC vaccine preparation could increase the antitumor effect of DC vaccines derived from mouse bone marrow. Our results showed that the migratory capacities of DCs were significantly increased after exposure to LDR. Furthermore, exposure to LDR resulted in an increased ability of DCs to induce T-cell proliferation, and the cytotoxic effect of cytotoxic T lymphocytes (CTLs) primed by the DCs exposed to LDR was significantly enhanced. An in vivo study using a mouse transplanted tumor model showed that subcutaneous injections of a DC vaccine exposed to LDR led to an increased mouse survival rate, infiltration of CTLs into tumor tissue, and apoptosis of tumor cells, which were accompanied by significant upregulation of serum interferon γ and interleukin 12. These results indicate that exposing DCs to LDR during the DC vaccine preparation is an effective approach to enhance its antitumor effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exposure to Low-Dose Radiation Enhanced the Antitumor Effect of a Dendritic Cell Vaccine

Wang¹,

Yu²,

He³

et al. 2019

Dose-Response

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“…DCs’ generation was performed as previously described by Zhu et al[ 25 ]. A concentrated leukocyte fraction was isolated from PBMCs that processed 200 mL of blood during each collection.…”

Section: Methodsmentioning

confidence: 99%

Dendritic cells engineered to secrete anti-DcR3 antibody augment cytotoxic T lymphocyte response against pancreatic cancerin vitro

Jiang¹,

Guo²,

Li³

et al. 2017

WJG

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AIMTo investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb).METHODSDCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR3 mAb on RNA-DCs’ viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR3 mAb secreting DCs was performed using a 51Cr releasing test. T cell responses induced by RNA-loaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12.RESULTSThe anti-DcR3 mAb secreted by DCs reacted with recombinant human DcR3 protein and generated a band with 35 kDa molecular weight. The secreting mAb was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DC-tumor-anti-DcR3 RNA for designated times, the DcR3 level in the supernatant of autologous PC cells was significantly down-regulated (P < 0.05). DCs secreting anti-DcR3 mAb could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA (P < 0.01). The anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA could enhance the induction of cytotoxic T lymphocytes (CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group (P < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T cells and CD8+ T cells incubated with anti-DcR3 mAb secreting DCs could produce extremely higher level IFN-γ and lower level IL4 than those incubated with DC-total tumor RNA or controls (P < 0.01).CONCLUSIONDCs engineered to secrete anti-DcR3 antibody can augment CTL responses against PC in vitro, and the immune-enhancing effects may be partly due to their capability of down-regulating DC apoptosis and adjusting the Th1/Th2 cytokine network.

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“…Maturation cocktails and other immunoadjuvants can be used to promote the immunostimulatory activity of exogenously activated DCs [6][7][8] . The nature of immunoadjuvants determines the type, the magnitude, the breadth, and the quality of antitumor immune response 9 .…”

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confidence: 99%

Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice

et al. 2020

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Treating large established tumors is challenging for dendritic cell (DC)-based immunotherapy. DC activation with tumor cell-derived exosomes (TEXs) carrying multiple tumorassociated antigen can enhance tumor recognition. Adding a potent adjuvant, high mobility group nucleosome-binding protein 1 (HMGN1), boosts DCs' ability to activate T cells and improves vaccine efficiency. Here, we demonstrate that TEXs painted with the functional domain of HMGN1 (TEX-N1ND) via an exosomal anchor peptide potentiates DC immunogenicity. TEX-N1ND pulsed DCs (DC TEX-N1ND) elicit long-lasting antitumor immunity and tumor suppression in different syngeneic mouse models with large tumor burdens, most notably large, poorly immunogenic orthotopic hepatocellular carcinoma (HCC). DC TEX-N1ND show increased homing to lymphoid tissues and contribute to augmented memory T cells. Importantly, N1ND-painted serum exosomes from cancer patients also promote DC activation. Our study demonstrates the potency of TEX-N1ND to strengthen DC immunogenicity and to suppress large established tumors, and thus provides an avenue to improve DC-based immunotherapy.

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Addition of CpG ODN and Poly (I:C) to a standard maturation cocktail generates monocyte-derived dendritic cells and induces a potent Th1 polarization with migratory capacity

Cited by 14 publications

References 64 publications

Exposure to Low-Dose Radiation Enhanced the Antitumor Effect of a Dendritic Cell Vaccine

Exposure to Low-Dose Radiation Enhanced the Antitumor Effect of a Dendritic Cell Vaccine

Dendritic cells engineered to secrete anti-DcR3 antibody augment cytotoxic T lymphocyte response against pancreatic cancerin vitro

Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice

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