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BETA
Nilsson, Berith
Alternative names
Publications (10 of 15) Show all publications
Idborg, H., Zandian, A., Sandberg, A., Truedsson, L., Nilsson, B., Elvin, K., . . . Jakobsson, P. (2018). Systemic lupus erythematosus subgroups, with features of antiphospholipid or Sjogren's syndrome, differ in molecular signatures and treatment perspectives. Scandinavian Journal of Rheumatology, 47, 2-2
Open this publication in new window or tab >>Systemic lupus erythematosus subgroups, with features of antiphospholipid or Sjogren's syndrome, differ in molecular signatures and treatment perspectives
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2018 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 2-2Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-363886 (URN)000442295400003 ()
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Sima, E., Nilsson, B., Nilsson Ekdahl, K. & Sundbom, M. (2017). Complement Proteins In Long-Term Weight Responders And Non-Responders After Gastric Bypass. In: IFSO 2017 22nd World Congress: . Paper presented at IFSO 2017 22nd World Congress (International federation for the surgery of obesity and metabolic disorders), 29 August - 2 September 2017, London, UK (pp. 679-679). Springer, 27
Open this publication in new window or tab >>Complement Proteins In Long-Term Weight Responders And Non-Responders After Gastric Bypass
2017 (English)In: IFSO 2017 22nd World Congress, Springer, 2017, Vol. 27, p. 679-679Conference paper, Poster (with or without abstract) (Other academic)
Place, publisher, year, edition, pages
Springer, 2017
Series
Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-347554 (URN)
Conference
IFSO 2017 22nd World Congress (International federation for the surgery of obesity and metabolic disorders), 29 August - 2 September 2017, London, UK
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2019-12-14Bibliographically 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
Jin, C., Fotaki, G., Ramachandran, M., Nilsson, B., Essand, M. & Yu, D. (2016). Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer. EMBO Molecular Medicine, 8(7), 702-711
Open this publication in new window or tab >>Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer
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2016 (English)In: EMBO Molecular Medicine, ISSN 1757-4676, E-ISSN 1757-4684, Vol. 8, no 7, p. 702-711Article in journal (Refereed) Published
Abstract [en]

Chimeric antigen receptor (CAR) T-cell therapy is a new successful treatment for refractory B-cell leukemia. Successful therapeutic outcome depends on long-term expression of CAR transgene in T cells, which is achieved by delivering transgene using integrating gamma retrovirus (RV) or lentivirus (LV). However, uncontrolled RV/LV integration in host cell genomes has the potential risk of causing insertional mutagenesis. Herein, we describe a novel episomal long-term cell engineering method using non-integrating lentiviral (NILV) vector containing a scaffold/matrix attachment region (S/MAR) element, for either expression of transgenes or silencing of target genes. The insertional events of this vector into the genome of host cells are below detection level. CD19 CAR T cells engineered with a NILV-S/MAR vector have similar levels of CAR expression as T cells engineered with an integrating LV vector, even after numerous rounds of cell division. NILV-S/MAR-engineered CD19 CAR T cells exhibited similar cytotoxic capacity upon CD19(+) target cell recognition as LV-engineered T cells and are as effective in controlling tumor growth in vivo We propose that NILV-S/MAR vectors are superior to current options as they enable long-term transgene expression without the risk of insertional mutagenesis and genotoxicity.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-300197 (URN)10.15252/emmm.201505869 (DOI)000383632300003 ()27189167 (PubMedID)
Funder
Swedish Childhood Cancer FoundationSwedish Cancer SocietySwedish Research CouncilGunnar Nilsson Cancer Foundation
Note

GT och MR delar på andraförfattarskapet.

Available from: 2016-08-05 Created: 2016-08-05 Last updated: 2018-01-10Bibliographically approved
Yu, D., Jin, C., Ramachandran, M., Xu, J., Nilsson, B., Korsgren, O., . . . Essand, M. (2013). Adenovirus Serotype 5 Vectors with Tat-PTD Modified Hexon and Serotype 35 Fiber Show Greatly Enhanced Transduction Capacity of Primary Cell Cultures. PLoS ONE, 8(1), e54952
Open this publication in new window or tab >>Adenovirus Serotype 5 Vectors with Tat-PTD Modified Hexon and Serotype 35 Fiber Show Greatly Enhanced Transduction Capacity of Primary Cell Cultures
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 1, p. e54952-Article in journal (Refereed) Published
Abstract [en]

Recombinant adenovirus serotype 5 (Ad5) vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus- receptor (CAR) on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection) show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-197480 (URN)10.1371/journal.pone.0054952 (DOI)000315210400045 ()
Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2017-12-06Bibliographically approved
Idborg, H., Rannar, S., Oliynyk, G., Forshed, J., Branca, R. M., Donten, M., . . . Jakobsson, P.-J. (2013). Stratification of sle Patients for Improved Diagnosis and Treatment. Annals of the Rheumatic Diseases, 72(S3), 466-466
Open this publication in new window or tab >>Stratification of sle Patients for Improved Diagnosis and Treatment
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2013 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, no S3, p. 466-466Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-221196 (URN)10.1136/annrheumdis-2013-eular.1398 (DOI)000331587903163 ()
Available from: 2014-03-26 Created: 2014-03-26 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
Fransson, M., Piras, E., Burman, J., Nilsson, B., Essand, M., Lu, B., . . . Loskog, A. S. (2012). CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery. Journal of Neuroinflammation, 9, 112
Open this publication in new window or tab >>CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery
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2012 (English)In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 9, p. 112-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proved to be beneficial, but generation of stable CNS-targeting Tregs needs further development. Here, we propose gene engineering to achieve CNS-targeting Tregs from naive CD4 cells and demonstrate their efficacy in the EAE model.

METHODS

CD4+T cells were modified utilizing a lentiviral vector system to express a chimeric antigen receptor (CAR) targeting myelin oligodendrocyte glycoprotein (MOG) in trans with the murine FoxP3 gene that drives Treg differentiation. The cells were evaluated in vitro for suppressive capacity and in C57BL/6 mice to treat EAE. Cells were administered by intranasal (i.n.) cell delivery.

RESULTS

The engineered Tregs demonstrated suppressive capacity in vitro and could efficiently access various regions in the brain via i.n cell delivery. Clinical score 3 EAE mice were treated and the engineered Tregs suppressed ongoing encephalomyelitis as demonstrated by reduced disease symptoms as well as decreased IL-12 and IFNgamma mRNAs in brain tissue. Immunohistochemical markers for myelination (MBP) and reactive astrogliosis (GFAP) confirmed recovery in mice treated with engineered Tregs compared to controls. Symptomfree mice were echallenged with a second EAE-inducing inoculum but remained healthy, demonstrating the sustained effect of engineered Tregs.

CONCLUSION

CNS-targeting Tregs delivered i.n. localized to the CNS and efficiently suppressed ongoing inflammation leading to diminished disease symptoms.

Keywords
MS, redirected cells, T regulatory cells, EAE, FoxP3, myelin oligodendrocyte glycoprotein
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-175383 (URN)10.1186/1742-2094-9-112 (DOI)000307014500001 ()22647574 (PubMedID)
Note

De två första författarna delar första författarskapet.

Available from: 2012-06-05 Created: 2012-06-05 Last updated: 2018-05-18Bibliographically approved
Hillerdal, V., Nilsson, B., Carlsson, B., Eriksson, F. & Essnd, M. (2012). T cells engineered with a T cell receptor against the prostate antigen TARP specifically kill HLA-A2+ prostate and breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 109(39), 15877-15881
Open this publication in new window or tab >>T cells engineered with a T cell receptor against the prostate antigen TARP specifically kill HLA-A2+ prostate and breast cancer cells
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2012 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 39, p. 15877-15881Article in journal (Refereed) Published
Abstract [en]

To produce genetically engineered T cells directed against prostate and breast cancer cells, we have cloned the T-cell receptor recognizing the HLA-A2–restricted T-cell recptor γ-chain alternate reading-frame protein (TARP)4–13 epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. Peripheral blood T cells transduced with a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptide-specific stimuli. These cells exerted peptide-specific IFN-γ production and cytotoxic activity. Importantly, HLA-A2+ prostate and breast cancer cells expressing TARP were also killed, demonstrating that the TARP4–13 epitope is a physiologically relevant target for T-cell therapy of prostate and breast cancer. In conclusion, we present the cloning of a T cell receptor (TCR) directed against a physiologically relevant HLA-A2 epitope of TARP. To our knowledge this report on engineering of T cells with a TCR directed against an antigen specifically expressed by prostate cells is unique.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-181199 (URN)10.1073/pnas.1209042109 (DOI)000309604500071 ()
Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2017-12-07Bibliographically 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
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