Transcriptional Targeting of Mature Dendritic Cells with Adenoviral Vectors via a Modular Promoter System for Antigen Expression and Functional Manipulation

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Knippertz I, Deinzer A, Dörrie J, Schaft N, Nettelbeck DM, Steinkasserer A
Zeitschrift: International Journal of Microbiology and Immunology Research
Jahr der Veröffentlichung: 2016
Band: 2016
Seitenbereich: 6078473-
ISSN: 2327-7769


Abstract

To specifically target dendritic cells (DCs) to simultaneously express different therapeutic transgenes for inducing immune responses against tumors, we used a combined promoter system of adenoviral vectors. We selected a 216 bp short Hsp70B'. core promoter induced by a mutated, constitutively active heat shock factor (mHSF) 1 to drive strong gene expression of therapeutic transgenes Melan A, BclxL, and IL-12p70 in HeLa cells, as well as in mature DCs ( mDCs). As this involves overexpressing mHSF1, we first evaluated the resulting effects on DCs regarding upregulation of heat shock proteins and maturation markers, toxicity, cytokine profile, and capacity to induce antigen-specific CD8+ T cells. Second, we generated the two-vector-based "modular promoter" system, where one vector contains the mHSF1 under the control of the human CD83 promoter, which is specifically active only in DCs and after maturation. mHSF1, in turn, activates the Hsp70B.. core promotor-driven expression of transgenes MelanA and IL-12p70 in the DC-like cell line XS52 and in human mature and hence immunogenic DCs, but not in tolerogenic immature DCs. These in vitro experiments provide the basis for an in vivo targeting of mature DCs for the expression of multiple transgenes. Therefore, this modular promoter system represents a promising tool for future DC-based immunotherapies in vivo.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Deinzer, Anja Dr. med.
Allgemeinmedizinisches Institut
Dörrie, Jan PD Dr.
Hautklinik
Steinkasserer, Alexander Prof. Dr.
Professur für Experimentelle Dermatologie


Einrichtungen weiterer Autorinnen und Autoren

Deutsches Krebsforschungszentrum (DKFZ)


Zitierweisen

APA:
Knippertz, I., Deinzer, A., Dörrie, J., Schaft, N., Nettelbeck, D.M., & Steinkasserer, A. (2016). Transcriptional Targeting of Mature Dendritic Cells with Adenoviral Vectors via a Modular Promoter System for Antigen Expression and Functional Manipulation. International Journal of Microbiology and Immunology Research, 2016, 6078473-.

MLA:
Knippertz, Ilka, et al. "Transcriptional Targeting of Mature Dendritic Cells with Adenoviral Vectors via a Modular Promoter System for Antigen Expression and Functional Manipulation." International Journal of Microbiology and Immunology Research 2016 (2016): 6078473-.

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Zuletzt aktualisiert 2018-29-11 um 08:23