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Leja, Justyna
Alternative names
Publications (10 of 13) Show all publications
Fletcher, E. A. K., Eltahir, M., Lindqvist, F., Rieth, J., Törnqvist, G., Leja-Jarblad, J. & Mangsbo, S. (2018). Extracorporeal human whole blood in motion, as a tool to predict first-infusion reactions and mechanism-of-action of immunotherapeutics. International Immunopharmacology, 54, 1-11
Open this publication in new window or tab >>Extracorporeal human whole blood in motion, as a tool to predict first-infusion reactions and mechanism-of-action of immunotherapeutics
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2018 (English)In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 54, p. 1-11Article in journal (Refereed) Published
Abstract [en]

First infusion reactions along with severe anaphylactic responses can occur as a result of systemic administration of therapeutic antibodies. The underlying mechanisms by which monoclonal antibodies induce cytokine release syndrome (CRS) can involve direct agonistic effects via the drug target, or a combination of target-engagement along with innate receptor interactions. Despite the wide variety of pathways and cells that can play a role in CRS, many currently used assays are devoid of one or more components that must be present for these responses to occur. One assay that has not been assessed for its capacity to predict CRS is the modified Chandler loop model. Herein we evaluate a plethora of commercially available monoclonal antibodies to evaluate the modified Chandler loop model's potential in CRS prediction. We demonstrate that in a 4-hour loop assay, both the superagonistic antibodies, anti-CD3 (OKT3) and anti-CD28 (ANC28.1), display a clear cytokine response with a mixed adaptive/innate cytokine source. OKT3 induce TNFα and IFN-γ release in 20 out of 23 donors tested, whereas ANC28.1 induce TNF-α, IL-2 and IFN-γ release in all donors tested (n = 18–22). On the other hand, non-agonistic antibodies associated with no or low infusion reactions in the clinic, namely cetuximab and natalizumab, neither induce cytokine release nor cause false positive responses. A TGN1412-like antibody also display a clear cytokine release with an adaptive cytokine profile (IFN-γ and IL-2) and all donors (n = 9) induce a distinct IL-2 response. Additionally, the value of an intact complement system in the assay is highlighted by the possibility to dissect out the mechanism-of-action of alemtuzumab and rituximab. The loop assay can either complement lymph node-like assays or stand-alone to investigate drug/blood interactions during preclinical development, or for individual safety screening prior to first-in-man clinical trial.

Keywords
Cytokine release syndrome, CRS, Immunotoxicity, Cytokine release assay, Anti-CD28, Alemtuzumab, OKT3
National Category
Immunology in the medical area Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-346359 (URN)10.1016/j.intimp.2017.10.021 (DOI)000423887900001 ()29100032 (PubMedID)
Funder
Swedish Research Council, K2013-79X-22263-01-2Swedish Society for Medical Research (SSMF)
Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2018-03-16Bibliographically approved
Yu, D., Leja, J., Loskog, A. S., Hellman, P., Giandomenico, V., Öberg, K. & Essand, M. (2017). Preclinical Evaluation of AdVince, an Oncolytic Adenovirus Adapted for Treatment of Liver Metastases from Neuroendocrine Cancer. Neuroendocrinology, 105(1), 54-66
Open this publication in new window or tab >>Preclinical Evaluation of AdVince, an Oncolytic Adenovirus Adapted for Treatment of Liver Metastases from Neuroendocrine Cancer
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2017 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 1, p. 54-66Article in journal (Refereed) Published
Abstract [en]

Cancer immunotherapy is becoming a cornerstone in the clinical care of cancer patients due to the breakthrough trials with immune checkpoint blockade antibodies and chimeric antigen receptor T cells. The next breakthrough in cancer immunotherapy is likely to be oncolytic viruses engineered to selectively kill tumor cells and deceive the immune system to believe that the tumor is a foreign entity that needs to be eradicated. We have developed AdVince, an oncolytic adenovirus for treatment of liver metastases from neuroendocrine tumor (NET). AdVince includes the gene promoter from human chromogranin A for selective replication in neuroendocrine cells, miR122 target sequences for reduced liver toxicity, and a cell-penetrating peptide in the capsid for increased infectivity of tumor cells and optimized spread within tumors. This paper describes the preclinical evaluation of AdVince on freshly isolated human gastrointestinal NET cells resected from liver metastases and freshly isolated human hepatocytes as well as in fresh human blood. AdVince selectively replicates in and kills NET cells. Approximately, 73-fold higher concentration of AdVince is needed to induce similar level of cytotoxicity in NET cells as in hepatocytes. AdVince did not activate complement or induce considerable amount of proinflammatory cytokines or chemokines in human blood. The data presented herein indicate that AdVince can be safely evaluated in a phase I/IIa clinical trial for patients with liver-dominant NET.

Place, publisher, year, edition, pages
S. Karger, 2017
Keywords
Neuroendocrine cancer; Oncolytic adenovirus; AdVince; Liver metastases; Immunotherapy
National Category
Neurology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-308877 (URN)10.1159/000448430 (DOI)000403362100006 ()27442441 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2019-02-27Bibliographically 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, p. 1519-1530Article 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
Keywords
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
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
Hillerdal, V., Ramachandran, M., Leja, J. & Essand, M. (2014). Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice. BMC Cancer, 14, 30
Open this publication in new window or tab >>Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice
2014 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, p. 30-Article in journal (Refereed) Published
Abstract [en]

Background:

Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer.

Methods:

We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 zeta signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student's t-test), proliferation (paired Student's t-test), CD107a expression (paired Student's t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves).

Results:

PSCA-CAR T cells exhibit specific interferon (IFN)-gamma and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice.

Conclusions:

Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer.

Keywords
CAR T cells, PSCA, Genetic engineering, Prostate cancer, Adoptive transfer
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-218943 (URN)10.1186/1471-2407-14-30 (DOI)000330050700001 ()
Available from: 2014-02-27 Created: 2014-02-20 Last updated: 2017-12-05Bibliographically approved
Jin, C., Yu, D., Čančer, M., Nilsson, B., Leja, J. & Essand, M. (2013). Tat‐PTD‐modified Oncolytic Adenovirus Driven by the SCG3 Promoter and ASH1 Enhancer for Neuroblastoma Therapy. Human Gene Therapy, 24(8), 766-775
Open this publication in new window or tab >>Tat‐PTD‐modified Oncolytic Adenovirus Driven by the SCG3 Promoter and ASH1 Enhancer for Neuroblastoma Therapy
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2013 (English)In: Human Gene Therapy, ISSN 1043-0342, E-ISSN 1557-7422, Vol. 24, no 8, p. 766-775Article in journal (Refereed) Published
Abstract [en]

Secretogranin III (SGC3) belongs to the granin family and is highly expressed in endocrine and neural tissues. The human SCG3 promoterhas not yet been characterized. We identified that a 0.5 kb DNA fragment upstream of the SCG3 gene can selectively drivetransgene expression in neuroblastoma cell lines. The strength of transgene expression was further increased and specificity maintained,by addition of the human achaete‐scute complex homolog 1 (ASH1) enhancer. We developed an oncolytic serotype 5‐basedadenovirus, where the SCG3 promoter and ASH1 enhancer drive E1A gene expression. The virus was further modified with a cellpenetratingpeptide (Tat‐PTD) in the virus capsid, which we have previously shown results in increased adenovirus transductionefficiency of many neuroblastoma cell lines. The virus, Ad5PTD(ASH1‐SCG3‐E1A), shows selective and efficient killing of neuroblastomacell lines in vitro, including cisplatin‐, etoposide‐ and doxorubicin‐insensitive neuroblastoma cells. Furthermore, it delays tumorgrowth and thereby prolonged survival for nude mice harboring subcutaneous human neuroblastoma xenograft. In conclusion, wereport a novel oncolytic adenovirus with potential use for neuroblastoma therapy.

Keywords
Tat-PTD, neuroblastoma, cancer therapy, adenovirus
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Clinical Virology; Medical Virology; Molecular Biotechnology; Molecular Medicine
Identifiers
urn:nbn:se:uu:diva-203651 (URN)10.1089/hum.2012.132 (DOI)000323181200007 ()
Funder
Swedish Cancer Society, 10‐0105Swedish Cancer Society, 10‐0552Swedish Research Council, K2013‐55X‐22191‐01‐3
Note

De två (2) första författarna delar förstaförfattarskapet.

Other funds:

TheSwedish Cancer Society (10‐0105 and 10‐0552), the Swedish ChildrenCancer Foundation (PROJ10/027, NBCNSPDHEL10/013,JIN C. ET AL. 20138PROJ11/062), Gunnar Nilsson’s Cancer Foundation, the SwedishResearch Council (K2013‐55X‐22191‐01‐3) and the Marcus andMarianne Wallenberg’s Foundation.

Available from: 2013-07-16 Created: 2013-07-16 Last updated: 2017-12-06Bibliographically approved
Yu, D., Jin, C., Leja, J., Majdalani, N., Nilsson, B., Eriksson, F. & Essand, M. (2011). Adenovirus with Hexon Tat-Protein Transduction Domain Modification Exhibits Increased Therapeutic Effect in Experimental Neuroblastoma and Neuroendocrine Tumors. Journal of Virology, 85(24), 13114-13123
Open this publication in new window or tab >>Adenovirus with Hexon Tat-Protein Transduction Domain Modification Exhibits Increased Therapeutic Effect in Experimental Neuroblastoma and Neuroendocrine Tumors
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2011 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 85, no 24, p. 13114-13123Article in journal (Refereed) Published
Abstract [en]

Adenovirus serotype 5 (Ad5) is widely used as an oncolytic agent for cancer therapy. However, its infectivity is highly dependent on the expression level of coxsackievirus-adenovirus receptor (CAR) on the surfaces of tumor cells. Furthermore, infected cells overproduce adenovirus fiber proteins, which are released prior to cell lysis. The released fibers block CAR on noninfected neighboring cells, thereby preventing progeny virus entry. Our aim was to add a CAR-independent infection route to Ad5 to increase the infectivity of tumor cells with low CAR expression and prevent the fiber-masking problem. We constructed Ad5 viruses that encode the protein transduction domain (PTD) of the HIV-1 Tat protein (Tat-PTD) in hypervariable region 5 (HVR5) of the hexon protein. Tat-PTD functions as a cell-penetrating peptide, and Tat-PTD-modified Ad5 showed a dramatic increased transduction of CAR-negative cell lines compared to unmodified vector. Moreover, while tumor cell infectivity was severely reduced for Ad5 in the presence of fiber proteins, it was only marginally reduced for Tat-PTD-modified Ad5. Furthermore, because of the sequence alteration in the hexon HVR, coagulation factor X-mediated virus uptake was significantly reduced. Mice harboring human neuroblastoma and neuroendocrine tumors show suppressed tumor growths and prolonged survival when treated with Tat-PTD-modified oncolytic viruses. Our data suggest that modification of Ad5 with Tat-PTD in HVR5 expands its utility as an oncolytic agent.

Keywords
adenovirus, cell penetrating peptide, Tat-PTD, neuroblastoma, neuroendocrine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-165614 (URN)10.1128/JVI.05759-11 (DOI)000297642000029 ()
Funder
Swedish Research Council, K2008-68X-15270-04-3
Available from: 2012-01-16 Created: 2012-01-09 Last updated: 2018-06-04Bibliographically approved
Leja, J., Yu, D., Nilsson, B., Gedda, L., Zieba, A., Hakkarainen, T., . . . Essand, M. (2011). Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells. Gene Therapy, 18(11), 1052-1062
Open this publication in new window or tab >>Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells
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2011 (English)In: Gene Therapy, ISSN 0969-7128, E-ISSN 1476-5462, Vol. 18, no 11, p. 1052-1062Article in journal (Refereed) Published
Abstract [en]

We have previously described the oncolytic adenovirus, Ad(CgA-E1A-miR122), herein denoted Ad5(CgA-E1A-miR122) that selectively replicates in and kills neuroendocrine cells, including freshly isolated midgut carcinoid cells from liver metastases. Ad5(CgA-E1A-miR122) is based on human adenovirus serotype 5 (Ad5) and infects target cells by binding to the coxsackie-adenovirus receptor (CAR) and integrins on the cell surface. Some neuroendocrine tumor (NET) and neuroblastoma cells express low levels of CAR and are therefore poorly transduced by Ad5. However, they often express high levels of somatostatin receptors (SSTRs). Therefore, we introduced cyclic peptides, which contain four amino acids (FWKT) and mimic the binding site for SSTRs in the virus fiber knob. We show that FWKT-modified Ad5 binds to SSTR2 on NET cells and transduces midgut carcinoid cells from liver metastases about 3-4 times better than non-modified Ad5 while it transduces normal hepatocytes at about 50% of Ad5. Moreover, FWKT-modified Ad5 overcomes neutralization in an ex vivo human blood loop model to greater extent than Ad5, indicating that fiber knob modification may prolong the systematic circulation time. We conclude that modification of adenovirus with the FWKT motif may be beneficial for NET therapy.

Keywords
oncolytic adenovirus, somatostatin, neuroendocrine tumors, carcinoid, neuroblastoma, proximity ligation
National Category
Cell and Molecular Biology Cancer and Oncology Microbiology in the medical area
Research subject
Oncology; Molecular Medicine
Identifiers
urn:nbn:se:uu:diva-146964 (URN)10.1038/gt.2011.54 (DOI)000296889500004 ()21490682 (PubMedID)
Available from: 2011-02-22 Created: 2011-02-22 Last updated: 2018-12-04
Leja, J. (2011). Oncolytic Adenovirus Therapy of Neuroendocrine Tumors. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Oncolytic Adenovirus Therapy of Neuroendocrine Tumors
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neuroendocrine tumors (NETs), originally described as carcinoids, represent a rare and heterogeneous group of neoplasms associated with intensive secretion of hormones, bioactive peptides and amines. Most of the patients are diagnosed at a late stage of disease, often with liver metastases. Surgery remains the main treatment to control metastatic disease, but is not curative. Oncolytic virotherapy represents a promising approach to treat cancer and different strategies have been exploited to restrict viral replication to tumor cells. We developed an oncolytic adenovirus based on serotype 5, Ad5[CgA-E1A], where the chromogranin A (CgA) promoter controls expression of the E1A gene and thereby virus replication. We found that Ad5[CgA-E1A], selectively replicates in NET cells and it is able to suppress fast-growing human BON carcinoid tumors in nude mice. The activity of Ad5[CgA-E1A] was not completely blocked in liver cells. We further repressed virus replication in hepatocytes by targeting E1A with miR122, an miRNA specifically expressed in the liver. miRNAs bind to mRNA and induce its cleavage or translational blockage. By insertion of tandem repeats of miR122 target sequences in 3’UTR of E1A gene, we observed reduced E1A protein expression and replication arrest in miR122 expressing liver cells. The oncolytic potency of the miR122-targeted virus was not affected in NET cells. Since some NET and neuroblastoma cells express high levels of somatostatin receptors (SSTRs), we introduced in the virus fiber knob cyclic peptides, which contain four amino acids (FWKT) and mimic the binding site of somatostatin for SSTRs. The FWKT-modified Ad5 transduces midgut carcinoid cells from liver metastases about 3-4 times better than non-modified Ad5. Moreover, FWKT-modified Ad5 overcomes neutralization in an ex vivo human blood loop model to a greater extent than Ad5, indicating that the fiber knob modification may prolong the systemic circulation time. NETs represent a huge therapeutic challenge and novel diagnostic markers are needed for early detection and effective treatment of NETs. We have profiled primary tumors and liver metastases of ileocaceal NETs, using Affymetrix microarrays and advanced bioinformatics. We have identified six novel marker genes and show high similarity between primary lesions and liver metastases transcriptome by hierarchical clustering analysis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. p. 60
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 653
Keywords
adenovirus, virotherapy, oncolytic virus, neuroendocrine tumors, chromogranin A, somatostatin receptors, microRNA, novel biomarkers
National Category
Cell and Molecular Biology Cancer and Oncology Microbiology in the medical area Cell and Molecular Biology
Research subject
Medical Science; Oncology; Medical Virology; Molecular Cellbiology
Identifiers
urn:nbn:se:uu:diva-146966 (URN)978-91-554-8022-6 (ISBN)
Public defence
2011-04-15, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2011-03-25 Created: 2011-02-22 Last updated: 2018-01-12Bibliographically approved
Essand, M., Leja, J., Giandomenico, V. & Öberg, K. E. (2011). Oncolytic Viruses for the Treatment of Neuroendocrine Tumors. Hormone and Metabolic Research, 43(12), 877-883
Open this publication in new window or tab >>Oncolytic Viruses for the Treatment of Neuroendocrine Tumors
2011 (English)In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 43, no 12, p. 877-883Article, review/survey (Refereed) Published
Abstract [en]

Oncolytic viruses are emerging as anticancer agents, and they have also shown great promise for use against neuroendocrine tumors. Many viruses have a natural tropism for replication in tumor cells. Others can be genetically engineered to selectively kill tumor cells. Viruses have some advantages as therapeutic agents over current cytotoxic drugs and small molecules. They replicate in tumor cells and thereby increase in number over time leading to increased dosage. They are immunogenic and can alter the immunosuppressive tumor microenvironment and activate immune effector cells. They have also been shown to be able to kill drug-resistant cancer stem cells. This article reviews the recent literature on oncolytic viruses used so far for neuroendocrine tumors and indicates important issues to focus on in the future.

Keywords
virotherapy; oncolytic virus; neuroendocrine tumors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-154561 (URN)10.1055/s-0031-1277225 (DOI)000297785500010 ()21626470 (PubMedID)
Available from: 2011-06-07 Created: 2011-06-07 Last updated: 2018-05-29Bibliographically approved
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