ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Genetic targeting of the active transcription factor XBP1s to dendritic cells potentiates vaccine-induced prophylactic and therapeutic antitumor immunity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Immunologic Crosstalk of Endoplasmic Reticulum Stress Signaling in Bladder Cancer.Current cancer drug targets · 2024Review
- Control of immune cell function by the unfolded protein response.Nature reviews. Immunology · 2023Review
- Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function.Science immunology · 2022Article
- Skin immunization for effective treatment of multifocal melanoma refractory to PD1 blockade and Braf inhibitors.Journal for immunotherapy of cancer · 2021Article
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- Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications.The FEBS journal · 2019Review
- IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8Frontiers in immunology · 2018Article
- Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma.Frontiers in immunology · 2017Review
- Genetic Immunization With In Vivo Dendritic Cell-targeting Liposomal DNA Vaccine Carrier Induces Long-lasting Antitumor Immune Response.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Genetic vaccines to potentiate the effective CD103+ dendritic cell-mediated cross-priming of antitumor immunity.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Dendritic cell-derived interleukin-15 is crucial for therapeutic cancer vaccine potency.Oncoimmunology · 2014Article
- Cellular immunotherapy for carcinoma using genetically modified EGFR-specific T lymphocytes.Neoplasia (New York, N.Y.) · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In vivo dendritic cells (DC) targeting is an attractive approach with potential advantages in vaccine efficacy, cost, and availability. Identification of molecular adjuvants to in vivo "modulate " DC to coordinately render improved Th1 and CD8 T cell immunity, and attenuated deleterious Treg effects, is a critical challenge. Here, we report that in vivo genetic targeting of the active transcription factor XBP1s to DC (XBP1s/DC) potentiated vaccine-induced prophylactic and therapeutic antitumor immunity in multiple tumor models. This immunization strategy is based on a genetic vaccine encoding both cytomegalovirus (CMV)-driven vaccine Aghsp70 and DC-specific CD11c-driven XBP1s. The novel targeted vaccine induced durable Th1 and CD8 T cell responses to poorly immunogenic self/tumor antigen (Ag) and attenuated tumor-associated Treg suppressive function. Bone marrow (BM)-derived DC genetically modified to simultaneously overexpress XBP1s and express Aghsp70 upregulated CD40, CD70, CD86, interleukin (IL)-15, IL-15Rα, and CCR7 expression, and increased IL-6, IL-12, and tumor necrosis factor (TNF)-α production in vitro. XBP1s/DC elevated functional DEC205(+)CD8α(+)DC in the draining lymph nodes (DLN). The data suggest a novel role for XBP1s in modulating DC to potentiate tumor vaccine efficacy via overcoming two major obstacles to tumor vaccines (i.e., T cell hyporesponsiveness against poorly immunologic self/tumor Ag and tumor-associated Treg-mediated suppression) and improving DEC205(+)CD8α(+)DC.
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