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Wenthe, Jessica
Publications (10 of 12) Show all publications
Eriksson, E., Milenova, I., Wenthe, J., Moreno, R., Ullenhag, G., Dimberg, A., . . . Loskog, A. S. (2017). Activating CD40 While Inhibiting IL6R Induces Cytokine Production without PDL1 Upregulation in DCs. Paper presented at 20th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 10-13, 2017, Washington, DC. Molecular Therapy, 25(5 S1), 54-54
Open this publication in new window or tab >>Activating CD40 While Inhibiting IL6R Induces Cytokine Production without PDL1 Upregulation in DCs
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2017 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 25, no 5 S1, p. 54-54Article in journal, Meeting abstract (Other academic) Published
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-331371 (URN)000401083600113 ()
Conference
20th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 10-13, 2017, Washington, DC
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Schiza, A., Wenthe, J., Mangsbo, S., Svensson, E., Nilsson, A., Tötterman, T., . . . Ullenhag, G. (2017). Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients. Journal of Translational Medicine, 15(79)
Open this publication in new window or tab >>Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients
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2017 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 15, no 79Article in journal (Refereed) Published
Abstract [en]

Background and aims: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). Methods: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide. Cells were analyzed by flow cytometry while plasma samples were analyzed by a multi-array proteomics. Results: All patients had an increased Teffector/Tregulatory cell ratio post therapy. Simultaneously, the death receptors TNFR1 and TRAIL-R2 were significantly up-regulated post treatment. Stem cell factor (SCF), E-selectin, and CD6 correlated to enhanced overall survival while a high level of granulocytic myeloid-derived suppressor cells (gMDSCs), IL8, IL10, TGFb1, CCL4, PlGF and Fl3t ligand was highest in patients with short survival. Conclusions: AdCD40L intratumoral injection induced desirable systemic immune effects that correlated to prolonged survival. Further studies using CD40 stimulation in malignant melanoma are warranted.

Keywords
AdCD40L, Malignant melanoma, Immunotherapy, Proteomics, T regulatory cells, Myeloid-derived suppressor cells
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-322800 (URN)10.1186/s12967-017-1182-z (DOI)000399786900002 ()28427434 (PubMedID)
Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2018-02-20Bibliographically approved
Schiza, A., Wenthe, J., Mangsbo, S., Eriksson, E., Nilsson, A., Tötterman, T., . . . Ullenhag, G. (2017). Adenovirus-mediated CD40L gene transfer increases teffector/tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 337-337
Open this publication in new window or tab >>Adenovirus-mediated CD40L gene transfer increases teffector/tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 337-337Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-346969 (URN)000411865200209 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-03-28Bibliographically approved
Eriksson, E., Milenova, I., Wenthe, J., Moreno, R., Alemany, R. & Loskog, A. S. (2017). An oncolytic virus targeting desmoplasia and immune activation in pancreatic cancer. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 335-335
Open this publication in new window or tab >>An oncolytic virus targeting desmoplasia and immune activation in pancreatic cancer
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 335-335Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-346968 (URN)000411865200204 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-03-28Bibliographically approved
Hoffmann, J.-M. -., Stock, S., Sellner, L., Hueckelhoven, A., Wang, L., Schmitt, A., . . . Schmitt, M. (2017). Distinct phenotype of CD19-specific CAR T cells generated from healthy donor vs. patient lymphocytes using either IL-7/IL-15 or IL-2. ONCOLOGY RESEARCH AND TREATMENT, 40, 213-213
Open this publication in new window or tab >>Distinct phenotype of CD19-specific CAR T cells generated from healthy donor vs. patient lymphocytes using either IL-7/IL-15 or IL-2
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2017 (English)In: ONCOLOGY RESEARCH AND TREATMENT, ISSN 2296-5270, Vol. 40, p. 213-213Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346555 (URN)000411428400514 ()
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-03-21Bibliographically approved
Lövgren, T., Wenthe, J., Karlsson, S. C., Gammelgård, G., Essand, M., Savoldo, B., . . . Loskog, A. (2017). Immunological biomarkers correlate to survival in CAR19-treated patients. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 337-337
Open this publication in new window or tab >>Immunological biomarkers correlate to survival in CAR19-treated patients
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 337-337Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346970 (URN)000411865200208 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27Bibliographically approved
Irenaeus, S., Schiza, A., Mangsbo, S. M., Wenthe, J., Svensson, E., Krause, J., . . . Ullenhag, G. (2017). Local irradiation does not enhance the effect of immunostimulatory AdCD40L gene therapy combined with low dose cyclophosphamide in melanoma patients. OncoTarget, 8(45), 78573-78587
Open this publication in new window or tab >>Local irradiation does not enhance the effect of immunostimulatory AdCD40L gene therapy combined with low dose cyclophosphamide in melanoma patients
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 45, p. 78573-78587Article in journal (Refereed) Published
Abstract [en]

Background: AdCD40L is an immunostimulatory gene therapy under evaluation for advanced melanoma, including ocular melanoma. Herein, we present the final data of a Phase I/IIa trial using AdCD40L alone or in combination with low dose cyclophosphamide +/- radiation therapy.

Methods: AdCD40L is a replication-deficient adenovirus carrying the gene for CD40 ligand (CD40L). Twenty-four patients with advanced melanoma were enrolled and treated with AdCD40L monotherapy, or combined with cyclophosphamide +/- single fraction radiotherapy. The patients were monitored for 10 weeks using immunological and radiological evaluations and thereafter for survival.

Results: AdCD40L treatment was safe and well tolerated both alone and in combination with cyclophosphamide as well as local radiotherapy. Four out of twenty-four patients had >1 year survival. Addition of cyclophosphamide was beneficial but adding radiotherapy did not further extend survival. High initial plasma levels of IL12 and MIP3b correlated to overall survival, whereas IL8 responses post-treatment correlated negatively with survival. Interestingly, antibody reactions to the virus correlated negatively with post IL6 and pre IL1b levels in blood.

Conclusions: AdCD40L was safely administered to patients and effect was improved by cyclophosphamide but not by radiotherapy. Immune activation profile at baseline may predict responders better than shortly after treatment.

Keywords
AdCD40L, gene therapy, immunotherapy, irradiation, malignant melanoma
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-333305 (URN)10.18632/oncotarget.19750 (DOI)000412111300034 ()29108250 (PubMedID)
Available from: 2017-11-10 Created: 2017-11-10 Last updated: 2018-01-26Bibliographically approved
Svensson, E., Milenova, I., Wenthe, J., Ståhle, M., Leja-Jarblad, J., Ullenhag, G., . . . Loskog, A. S. (2017). Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus.. Clinical Cancer Research, 23(19), 5846-5857
Open this publication in new window or tab >>Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus.
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2017 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 19, p. 5846-5857Article in journal (Refereed) Published
Abstract [en]

Purpose: Pancreatic cancer is a severe indication with short expected survival despite surgery and/or combination chemotherapeutics. Checkpoint blockade antibodies are approved for several cancer indications, but pancreatic cancer has remained refractory. However, there are clinical data suggesting that stimulation of the CD40 pathway may be of interest for these patients. Oncolytic viruses armed with immunostimulatory genes represent an interesting approach. Herein, we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activates the CD40 and 4-1BB pathways, respectively. As many cells in the tumor stroma, including stellate cells and the infiltrating immune cells, express CD40 and some 4-1BB, we hypothesize that LOAd703 activates immunity and simultaneously modulates the biology of the tumor stroma.Experimental Design: Tumor, stellate, endothelial, and immune cells were infected by LOAd703 and investigated by flow cytometry, proteomics, and functional analyses.Results: LOAd703-infected pancreatic cell lines were killed by oncolysis, and the virus was more effective than standard-of-care gemcitabine. In in vivo xenograft models, LOAd703 efficiently reduced established tumors and could be combined with gemcitabine for additional effect. Infected stellate and tumor cells reduced factors that promote tumor growth (Spp-1, Gal-3, HGF, TGFβ and collagen type I), while chemokines were increased. Molecules involved in lymphocyte migration were upregulated on infected endothelial cells. Dendritic cells were robustly stimulated by LOAd703 to produce costimulators, cytokines and chemokines, and such DCs potently expanded both antigen-specific T cells and NK cells.Conclusions: LOAd703 is a potent immune activator that modulates the stroma to support antitumor responses. Clin Cancer Res; 1-12. ©2017 AACR.

National Category
Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-330158 (URN)10.1158/1078-0432.CCR-17-0285 (DOI)000412160500021 ()28536305 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-09-27 Created: 2017-09-27 Last updated: 2018-02-02Bibliographically approved
Enblad, G., Karlsson, H., Wenthe, J., Wikström, K. I., Essand, M., Savoldo, B., . . . Loskog, A. (2016). A Clinical Trial Using Third Generation CD19 Targeting CAR T Cells for Relapsed Lymphoma and Leukemia. Paper presented at 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 04-07, 2016, Washington, DC. Molecular Therapy, 24, S295-S296
Open this publication in new window or tab >>A Clinical Trial Using Third Generation CD19 Targeting CAR T Cells for Relapsed Lymphoma and Leukemia
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2016 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 24, p. S295-S296Article in journal, Meeting abstract (Other academic) Published
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-299273 (URN)000375264200736 ()
Conference
19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 04-07, 2016, Washington, DC
Available from: 2016-07-18 Created: 2016-07-18 Last updated: 2017-11-28Bibliographically approved
Wenthe, J., Eriksson, E., Milenova, I., Moreno, R., Alemany, R. & Loskog, A. (2016). A Novel Oncolytic Adenovirus Expressing Tumor Microenvironment Stimulators to Evoke and Facilitate Anti-Tumor Immune Responses. Paper presented at 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 04-07, 2016, Washington, DC. Molecular Therapy, 24, S206-S206
Open this publication in new window or tab >>A Novel Oncolytic Adenovirus Expressing Tumor Microenvironment Stimulators to Evoke and Facilitate Anti-Tumor Immune Responses
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2016 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 24, p. S206-S206Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-299276 (URN)000375264200510 ()
Conference
19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 04-07, 2016, Washington, DC
Available from: 2016-07-18 Created: 2016-07-18 Last updated: 2017-11-28Bibliographically approved
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