Generation of dendritic cell-based vaccines for cancer therapy

Reinhard, Günter; Märten, Angela; Kiske, S M; Feil, Fernanda; Bieber, Thomas; Schmidt‐Wolf, Ingo G.H.

doi:10.1038/sj.bjc.6600316

Cited by 46 publications

(35 citation statements)

References 33 publications

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“…17,18 Whereas AdRGD is advantageous for gene transduction, several reports suggest that viral vector-mediated gene transduction induces cell death in target cells. 30 Our present findings demonstrated that AdRGD-Bcl-x L -and AdRGD-Bclx FNK -treated DCs are more resistant to naturally occurring cell death than AdRGD-Luc, suggesting that the antiapoptotic gene-transfer strategy could improve the viral vector-induced DC death. Based on these observations, it should be possible to further enhance the potency of DC-based vaccines through the combined use of AdRGD-mediated Bcl-x L or Bcl-x FNK gene transduction technology with other vaccine-enhancement techniques, such as a chemokine receptor gene (CCR7)-transduction strategy for more efficient accumulation of DCs in regional LNs or inflammatory cytokine gene expression.…”

Section: Discussionsupporting

confidence: 51%

Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency

et al. 2008

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Dendritic cells (DCs) have a critical role in the induction of antigen-specific immune responses, transporting antigens from peripheral tissue to regional lymph nodes where they interact with antigen-specific T lymphocytes. Recent studies revealed that the efficacy of the T cell-dependent immune response depends on the lifespan of the antigen-presenting DCs in the lymph nodes. Here, we succeeded in engineering long-lived antigen-presenting DCs via Bcl-x L -derived hyperactive mutant antiapoptotic protein (Bcl-x FNK ) gene transfer. In a B16BL6 melanoma model, these long-lived DCs exerted potent antitumor immunity that depended mainly on antigenspecific cytotoxic T lymphocytes. Furthermore, in vivo longevity of the long-lived DC vaccine led to antigen-specific activation of interferon-g-producing CD4 + and CD8 + T cells. Thus, the long-lived DC vaccine strategy is highly useful for constructing DC vaccines, as well as other cell-based medicines, such as stem cell therapy.

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Section: Discussionsupporting

confidence: 51%

Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency

et al. 2008

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“…In general, these strategies consist in the isolation of DCs or DC precursors from patients to be then loaded with tumoral Ags followed by their in vitro maturation using different stimuli prior to their transfer into the patient. This approach has been demonstrated to be efficient for treating cancer or viral infections in many animal models (3)(4)(5)(6)(7)(8). However, clinical trials have shown that several variables (DC lineage, Ag loading to DCs, maturation stage of DCs, migration capacity, route of injection, number of DC injected, etc.…”

mentioning

confidence: 99%

The Extra Domain A from Fibronectin Targets Antigens to TLR4-Expressing Cells and Induces Cytotoxic T Cell Responses In Vivo

Lasarte

Casares

Gorraiz

et al. 2007

The Journal of Immunology

115

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Vaccination strategies based on the in vivo targeting of Ags to dendritic cells (DCs) are needed to improve the induction of specific T cell immunity against tumors and infectious agents. In this study, we have used a recombinant protein encompassing the extra domain A from fibronectin (EDA), an endogenous ligand for TLR4, to deliver Ags to TLR4-expressing DC. The purified EDA protein was shown to bind to TLR4-expressing HEK293 cells and to activate the TLR4 signaling pathway. EDA also stimulated the production by DC of proinflammatory cytokines such as IL-12 or TNF-α and induced their maturation in vitro and in vivo. A fusion protein between EDA and a cytotoxic T cell epitope from OVA efficiently presented this epitope to specific T cells and induced the in vivo activation of a strong and specific CTL response. Moreover, a fusion protein containing EDA and the full OVA also improved OVA presentation by DC and induced CTL responses in vivo. These EDA recombinant proteins protected mice from a challenge with tumor cells expressing OVA. These results strongly suggest that the fibronectin extra domain A may serve as a suitable Ag carrier for the development of antiviral or antitumoral vaccines.

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“…From that time, DCs have been utilized to treat various malignant diseases such as renal cancer, lymphoma, colorectal cancer and other diseases [25][26][27]. In previous investigations no association with a higher incidence of autoimmunity has been demonstrated in vaccination with tumor lysate-pulsed DCs compared with peptide-pulsed DCs [28] which may suggest the safety of this kind of vaccine.…”

Section: Discussionmentioning

confidence: 89%

Immunotherapy with tumor cell lysate-pulsed CD8α+ dendritic cells modulates intra-tumor and spleen lymphocyte subpopulations

Azadmehr

Aa²,

Amirghofran³

et al. 2013

neo

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Using cellular adjuvants including dendritic cells (DCs) has provided a promising approach in immunotherapy of cancer. Our previous study showed that mice immunization with tumor cell lysate-pulsed DCs (TL-CD8α+DCs) could significantly suppress the tumor growth and increase mice survival. The aim of the present study was to investigate the impact of TL-CD8α+DC vaccine on intra-tumor and spleen lymphocyte subpopulations in tumor-bearing mice. A Balb/c mouse model of fibrosarcoma was used and changes in various lymphocyte subpopulations including CD4 + , CD8+ and CD4T cells in mice immunized with TL-CD8α + DCs were studied. The cytotoxic activity of the lymphocytes and tumor growth inhibitory rate were also measured. Immunotherapy with TL-CD8α + DCs significantly enhanced both CD4+ and CD8+ lymphocytes, whereas decreased CD4 + CD25 + Foxp3 + regulatory T cells as well as the tumor growth rate. There was also a decrease in the ratio of regulatory T cells to CD4 + and to CD8 + lymphocytes in both the tumor and spleen tissues as compared to that in the non-immunized control mice. Immunization with TL-CD8α + DCs as well as CD8α + DCs significantly increased the splenocytes cytotoxic activity by 45.1% and 18.2% of control, respectively. In conclusion, the current study indicated that TL-CD8α + DCs can enhance tumor immunity against the fibrosarcoma by enhancing both the CD4 + and CD8 + lymphocytes and reducing regulatory T cells. This finding suggests the usefulness of TL-CD8α + DCs vaccine for cancer treatment.

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Generation of dendritic cell-based vaccines for cancer therapy

Cited by 46 publications

References 33 publications

Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency

Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency

The Extra Domain A from Fibronectin Targets Antigens to TLR4-Expressing Cells and Induces Cytotoxic T Cell Responses In Vivo

Immunotherapy with tumor cell lysate-pulsed CD8α+ dendritic cells modulates intra-tumor and spleen lymphocyte subpopulations

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