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Publications (10 of 69) Show all publications
Essand, M., Ma, J., Jin, C., Ramachandran, M. & Yu, D. (2017). CAR T-Cells with Induced Secretion of Helicobacter Pylori Neutrophil-Activating Protein (HP-NAP) Yields Improved Anti-Tumor Activity and Reduced Immunosuppression. 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), 288-288.
Open this publication in new window or tab >>CAR T-Cells with Induced Secretion of Helicobacter Pylori Neutrophil-Activating Protein (HP-NAP) Yields Improved Anti-Tumor Activity and Reduced Immunosuppression
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2017 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 25, no 5 S1, 288-288 p.Article 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-331372 (URN)000401083600621 ()
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
Martikainen, M., Ruotsalainen, J., Tuomela, J., Harkonen, P., Essand, M., Heikkila, J. & Hinkkanen, A. (2017). Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice. British Journal of Cancer, 117(1), 51-55.
Open this publication in new window or tab >>Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
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2017 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 117, no 1, 51-55 p.Article in journal (Refereed) Published
Abstract [en]

Background: Despite recent therapeutic and diagnostic advances, prostate cancer remains the second leading cause of cancer-related deaths among men in the Western world. Oncolytic viruses that replicate selectively in tumour cells represent a novel treatment candidate for these malignancies.

Methods: We analysed infectivity of avirulent Semliki Firest virus SFV-VA7 in human prostate cancer cell lines VCaP, LNCaP and 22Rv1 and in nonmalignant prostate epithelial cell line RWPE-1. Therapeutic potency of SFV-VA7 was evaluated in subcutaneous and orthotopic mouse LNCaP xenograft models.

Results: SFV-VA7 infected and killed the tested human prostate cancer cell lines irrespective of their hormone response status, while the nonmalignant prostate epithelial cell line RWPE-1 proved highly virus resistant. Notably, a single peritoneal dose of SFV-VA7 was sufficient to eradicate all subcutaneous and orthotopic LNCaP tumours.

Conclusions: Our results indicate that SFV-VA7 is a novel, promising therapeutic virus against prostate cancer warranting further testing in early clinical trials.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
Keyword
oncolytic virotherapy, alphavirus, semliki forest virus, prostate cancer, orthotopic tumour model, xenograft tumour model
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-329638 (URN)10.1038/bjc.2017.151 (DOI)000404111300007 ()28557974 (PubMedID)
Available from: 2017-09-26 Created: 2017-09-26 Last updated: 2017-09-26Bibliographically approved
Pan, G., Ameur, A., Enroth, S., Bysani, M., Nord, H., Cavalli, M., . . . Wadelius, C. (2017). PATZ1 down-regulates FADS1 by binding to rs174557 and is opposed by SP1/SREBP1c. Nucleic Acids Research, 45(5), 2408-2422.
Open this publication in new window or tab >>PATZ1 down-regulates FADS1 by binding to rs174557 and is opposed by SP1/SREBP1c
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2017 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 45, no 5, 2408-2422 p.Article in journal (Refereed) Published
Abstract [en]

The FADS1 and FADS2 genes in the FADS cluster encode the rate-limiting enzymes in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs). Genetic variation in this region has been associated with a large number of diseases and traits many of them correlated to differences in metabolism of PUFAs. However, the causative variants leading to these associations have not been identified. Here we find that the multiallelic rs174557 located in an AluYe5 element in intron 1 of FADS1 is functional and lies within a PATZ1 binding site. The derived allele of rs174557, which is the common variant in most populations, diminishes binding of PATZ1, a transcription factor conferring allele-specific downregulation of FADS1 The PATZ1 binding site overlaps with a SP1 site. The competitive binding between the suppressive PATZ1 and the activating complex of SP1 and SREBP1c determines the enhancer activity of this region, which regulates expression of FADS1.

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-317999 (URN)10.1093/nar/gkw1186 (DOI)000397286600024 ()27932482 (PubMedID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish Research Council, 521-2010-3505 6212011-6052 521-2012-2884Swedish Diabetes AssociationSwedish Cancer Society, 15 0878
Available from: 2017-03-23 Created: 2017-03-23 Last updated: 2017-04-18Bibliographically approved
Ramachandran, M., Yu, D., Dyczynski, M., Baskaran, S., Zhang, L., Lulla, A., . . . Essand, M. (2017). Safe and effective treatment of experimental neuroblastoma and glioblastoma using systemically administered triple microRNA-detargeted oncolytic Semliki Forest virus. Clinical Cancer Research, 23(6), 1519-1530.
Open this publication in new window or tab >>Safe and effective treatment of experimental neuroblastoma and glioblastoma using systemically administered triple microRNA-detargeted oncolytic Semliki Forest virus
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2017 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 6, 1519-1530 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE:

Glioblastoma multiforme (GBM) and high-risk neuroblastoma are cancers with poor outcome. Immunotherapy in the form of neurotropic oncolytic viruses is a promising therapeutic strategy for these malignancies. Here we evaluate the oncolytic potential of the neurovirulent and partly interferon (IFN)-β-resistant Semliki Forest virus (SFV)-4 in GBMs and neuroblastomas. To reduce neurovirulence we constructed SFV4miRT, which is attenuated in normal CNS cells through insertion of microRNA target sequences for miR124, miR125, miR134 Experimental Design:Oncolytic activity of SFV4miRT was examined in mouse neuroblastoma and GBM cell lines and in patient-derived human glioblastoma cell cultures (HGCC). In vivo neurovirulence and therapeutic efficacy was evaluated in two syngeneic orthotopic glioma models (CT-2A, GL261) and syngeneic subcutaneous neuroblastoma model (NXS2). The role of IFN-β in inhibiting therapeutic efficacy was investigated.

RESULTS:

The introduction of microRNA target sequences reduced neurovirulence of SFV4 in terms of attenuated replication in mouse CNS cells and ability to cause encephalitis when administered intravenously. A single intravenous injection of SFV4miRT prolonged survival and cured 4 of 8 mice (50%) with NXS2 and 3 of 11 mice (27%) with CT-2A, but not for GL261 tumor bearing mice. In vivo therapeutic efficacy in different tumor models inversely correlated to secretion of IFN-β by respective cells upon SFV4 infection in vitro Similarly, killing efficacy of HGCC lines inversely correlated to IFN-β response and interferon-α⁄β receptor (IFNAR)-1 expression.

CONCLUSIONS:

SFV4miRT has reduced neurovirulence, while retaining its oncolytic potential. SFV4miRT is an excellent candidate for treatment of GBMs and neuroblastomas with low IFN-β secretion.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2017
Keyword
Semliki Forest virus, Glioblastoma, Neuroblastoma, Oncolytic virus immunotherapy, Type-I antiviral response
National Category
Other Basic Medicine
Research subject
Oncology; Biology with specialization in Molecular Biotechnology
Identifiers
urn:nbn:se:uu:diva-303633 (URN)10.1158/1078-0432.CCR-16-0925 (DOI)000397344800018 ()27637889 (PubMedID)
Funder
Swedish Research Council, K2013-22191-01-3Swedish Cancer Society, CAN2013/373Swedish Childhood Cancer Foundation, PROJ12/082
Available from: 2016-09-21 Created: 2016-09-21 Last updated: 2018-01-10Bibliographically 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, S295-S296 p.Article 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
Fotaki, G., Jin, C., Karlsson-Parra, A., Yu, D. & Essand, M. (2016). Allogeneic dendritic cells (AlloDCs) transduced with an infection enhanced adenovirus as adjuvant for cancer immunotherapy. CANCER IMMUNOLOGY RESEARCH, 4(1).
Open this publication in new window or tab >>Allogeneic dendritic cells (AlloDCs) transduced with an infection enhanced adenovirus as adjuvant for cancer immunotherapy
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2016 (English)In: CANCER IMMUNOLOGY RESEARCH, ISSN 2326-6066, Vol. 4, no 1Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-299396 (URN)10.1158/2326-6074.CRICIMTEATIAACR15-A172 (DOI)000375484400309 ()
Available from: 2016-07-18 Created: 2016-07-18 Last updated: 2018-01-10Bibliographically approved
Hillerdal, V., Boura, V. F., Björkelund, H., Andersson, K. & Essand, M. (2016). Avidity characterization of genetically engineered T-cells with novel and established approaches. BMC Immunology, 17, Article ID 23.
Open this publication in new window or tab >>Avidity characterization of genetically engineered T-cells with novel and established approaches
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2016 (English)In: BMC Immunology, ISSN 1471-2172, E-ISSN 1471-2172, Vol. 17, 23Article in journal (Refereed) Published
Abstract [en]

Background: Adoptive transfer of genetically engineered autologous T-cells is becoming a successful therapy for cancer. The avidity of the engineered T-cells is of crucial importance for therapy success. We have in the past cloned a T-cell receptor (TCR) that recognizes an HLA-A2 (MHC class I)-restricted peptide from the prostate and breast cancer- associated antigen TARP. Herein we perform a side-by-side comparison of the TARP-specific TCR (TARP-TCR) with a newly cloned TCR specific for an HLA-A2-restricted peptide from the cytomegalovirus (CMV) pp65 antigen. Results: Both CD8(+) T-cells and CD4(+) T-cells transduced with the HLA-A2-restricted TARP-TCR could readily be detected by multimer analysis, indicating that the binding is rather strong, since binding occured also without the CD8 co-receptor of HLA-A2. Not surprisingly, the TARP-TCR, which is directed against a self-antigen, had weaker binding to the HLA-A2/peptide complex than the CMV pp65-specific TCR (pp65-TCR), which is directed against a viral epitope. Higher peptide concentrations were needed to achieve efficient cytokine release and killing of target cells when the TARP- TCR was used. We further introduce the LigandTracer technology to study cell-cell interactions in real time by evaluating the interaction between TCR-engineered T-cells and peptide-pulsed cancer cells. We were able to successfully detect TCR-engineered T-cell binding kinetics to the target cells. We also used the xCELLigence technology to analyzed cell growth of target cells to assess the killing potency of the TCR-engineered T-cells. T-cells transduced with the pp65 - TCR exhibited more pronounced cytotoxicity, being able to kill their targets at both lower effector to target ratios and lower peptide concentrations. Conclusion: The combination of binding assay with functional assays yields data suggesting that TARP- TCR-engineered T-cells bind to their target, but need more antigen stimulation compared to the pp65-TCR to achieve full effector response. Nonetheless, we believe that the TARP- TCR is an attractive candidate for immunotherapy development for prostate and/or breast cancer.

Keyword
T-cell receptor, Affinity, Avidity, LigandTracer, xCELLigence, HLA binding, TARP, CMV pp65
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-300454 (URN)10.1186/s12865-016-0162-z (DOI)000379892000001 ()27411667 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2016-08-09 Created: 2016-08-09 Last updated: 2018-01-10Bibliographically approved
Enblad, G., Karlsson, H., Wikström, K. I., Essand, M., Savoldo, B., Brenner, M. K., . . . Loskog, A. (2016). CD19-targeting third generation CAR T cells for relapsed and refractory lymphoma and leukemia: report from the Swedish phase Ulla trial. CANCER IMMUNOLOGY RESEARCH, 4(1).
Open this publication in new window or tab >>CD19-targeting third generation CAR T cells for relapsed and refractory lymphoma and leukemia: report from the Swedish phase Ulla trial
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2016 (English)In: CANCER IMMUNOLOGY RESEARCH, ISSN 2326-6066, Vol. 4, no 1Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-299395 (URN)10.1158/2326-6074.CRICIMTEATIAACR15-A041 (DOI)000375484400048 ()
Available from: 2016-07-18 Created: 2016-07-18 Last updated: 2018-01-10Bibliographically approved
Wu, C., Cao, X., Yu, D., Huijbers, E. J. M., Essand, M., Akusjärvi, G., . . . Svensson, C. (2016). HAdV-2-suppressed growth of SV40 T antigen-transformed mouse mammary epithelial cell-induced tumours in SCID mice. Virology, 489, 44-50.
Open this publication in new window or tab >>HAdV-2-suppressed growth of SV40 T antigen-transformed mouse mammary epithelial cell-induced tumours in SCID mice
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2016 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 489, 44-50 p.Article in journal (Refereed) Published
Abstract [en]

Human adenovirus (HAdV) vectors are promising tools for cancer therapy, but the shortage of efficient animal models for productive HAdV infections has restricted the evaluation of systemic effects to mainly immunodeficient mice. Previously, we reported a highly efficient replication of HAdV-2 in a non-tumorigenic mouse mammary epithelial cell line, NMuMG. Here we show that HAdV-2 gene expression and progeny formation in NMuMG cells transformed with the SV40 T antigen (NMuMG-T cells) were as efficient as in the parental NMuMG cells. Injection of HAdV-2 into tumours established by NMuMG-T in SCID mice caused reduced tumour growth and signs of intratumoural lesions. HAdV-2 replicated within the NMuMG-T-established tumours, but not in interspersed host-derived tissues within the tumours. The specific infection of NMuMG-T-derived tumours was verified by the lack of viral DNA in kidney, lung or spleen although low levels of viral DNA was occasionally found in liver.

Keyword
Oncolytic adenovirus, Murine cells, Anti-tumour activity, Permissive infection, Viral replication
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-282389 (URN)10.1016/j.virol.2015.11.031 (DOI)000370892100005 ()26707269 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2017-11-30Bibliographically approved
Jin, C., Ramachandran, M., Fotaki, G., Nilsson, B., Essand, M. & Yu, D. (2016). Long-term episomal gene transfer for safe engineering of T cells for adoptive cell therapy of cancer. CANCER IMMUNOLOGY RESEARCH, 4(1).
Open this publication in new window or tab >>Long-term episomal gene transfer for safe engineering of T cells for adoptive cell therapy of cancer
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2016 (English)In: CANCER IMMUNOLOGY RESEARCH, ISSN 2326-6066, Vol. 4, no 1Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-299397 (URN)10.1158/2326-6074.CRICIMTEATIAACR15-A171 (DOI)000375484400296 ()
Available from: 2016-07-18 Created: 2016-07-18 Last updated: 2018-01-10Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-9725-0422

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