uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Schiza, Aglaia
Alternative names
Publications (8 of 8) Show all publications
Lindman, H., Haji, A., Jernling, M. & Schiza, A. (2018). Evidence on the occurrence of brain metastases amongst deceased metastatic breast cancer patients from an Uppsala county disease registry. Paper presented at 11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN. European Journal of Cancer, 92, S118-S118
Open this publication in new window or tab >>Evidence on the occurrence of brain metastases amongst deceased metastatic breast cancer patients from an Uppsala county disease registry
2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 92, p. S118-S118Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-357178 (URN)000429103100318 ()
Conference
11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN
Available from: 2018-08-14 Created: 2018-08-14 Last updated: 2018-08-14Bibliographically 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
Show others...
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
Show others...
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
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
Show others...
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
Maleka, A., Åström, G., Bystrom, P. & Ullenhag, G. J. (2016). A case report of a patient with metastatic ocular melanoma who experienced a response to treatment with the BRAF inhibitor vemurafenib. BMC Cancer, 16, Article ID 634.
Open this publication in new window or tab >>A case report of a patient with metastatic ocular melanoma who experienced a response to treatment with the BRAF inhibitor vemurafenib
2016 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 16, article id 634Article in journal (Refereed) Published
Abstract [en]

Background: Conjunctival malignant melanoma (CMM) is a rare malignancy and in the advanced setting there is no effective treatment. In contrast, half of cutaneous melanomas have BRAF mutations and treatment with BRAF inhibitors is established for patients with disseminated disease. The most common form of ocular melanoma, uveal melanoma, lacks these mutations, however, their presence has been reported for CMM. Case presentation: We used the BRAF inhibitor vemurafenib to treat a 53 year-old female suffering from a BRAFV600E mutated metastatic CMM. The patient benefited from the treatment, a response was evident within a week and she experienced a progression free survival of four months. Conclusions: To our knowledge, this is the first described case of response to vemurafenib treatment in a patient with ocular melanoma.

Keywords
BRAF inhibitor, BRAF mutation, Conjunctival malignant melanoma, Ocular melanoma, Vemurafenib
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-305937 (URN)10.1186/s12885-016-2657-7 (DOI)000384169800001 ()27520988 (PubMedID)
Available from: 2016-11-11 Created: 2016-10-24 Last updated: 2018-02-20Bibliographically approved
Loskog, A., Maleka, A., Mangsbo, S., Svensson, E., Lundberg, C., Nilsson, A., . . . Ullenhag, G. (2016). Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients. British Journal of Cancer, 114(8), 872-880
Open this publication in new window or tab >>Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients
Show others...
2016 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 8, p. 872-880Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Current approaches for treating metastatic malignant melanoma (MM) are not effective enough and are associated with serious adverse events. Due to its immunogenicity, melanoma is an attractive target for immunostimulating therapy. In this phase I/IIa study, local AdCD40L immunostimulatory gene therapy was evaluated in patients with MM.

METHODS: AdCD40L is an adenovirus carrying the gene for CD40 ligand. Patients that failed standard treatments were enrolled. Six patients received four weekly intratumoral AdCD40L injections. Next, nine patients received low-dose cyclophosphamide conditioning before the first and fourth AdCD40L injection. The blood samples were collected at multiple time points for chemistry, haematology and immunology evaluations. Radiology was performed at enrolment and repeated twice after the treatment.

RESULTS: AdCD40L was safe with mild transient reactions. No objective responses were recorded by MRI, however, local and distant responses were seen on FDG-PET. The overall survival at 6 months was significantly better when cyclophosphamide was added to AdCD40L. The patients with the best survival developed the highest levels of activated T cells and experienced a pronounced decrease of intratumoral IL8.

CONCLUSIONS: AdCD40L therapy for MM was well tolerated. Local and distant responses along with better survival in the low-dose cyclophosphamide group are encouraging.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-295735 (URN)10.1038/bjc.2016.42 (DOI)000374129200004 ()27031851 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2016-06-09 Created: 2016-06-09 Last updated: 2018-02-20Bibliographically approved
Loskog, A., Maleka, A., Mangsbo, S., Svensson, E., Krause, J., Agnarsdottir, M., . . . Ullenhag, G. (2014). AdCD40L Immunostimulatory Gene Therapy in Combination with Cyclophosphamide Prolongs 6-Months Survival in a Phase I/II Trial for Malignant Melanoma. Paper presented at 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 21-24, 2014, Washington, DC. Molecular Therapy, 22, S247-S247
Open this publication in new window or tab >>AdCD40L Immunostimulatory Gene Therapy in Combination with Cyclophosphamide Prolongs 6-Months Survival in a Phase I/II Trial for Malignant Melanoma
Show others...
2014 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 22, p. S247-S247Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-228909 (URN)000337231300633 ()
Conference
17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 21-24, 2014, Washington, DC
Available from: 2014-07-22 Created: 2014-07-22 Last updated: 2018-01-11Bibliographically approved
Maleka, A., Enblad, G., Sjörs, G., Lindqvist, A. & Ullenhag, G. (2013). Treatment of metastatic malignant melanoma with vemurafenib during pregnancy. Journal of Clinical Oncology, 31(11), e192-e193
Open this publication in new window or tab >>Treatment of metastatic malignant melanoma with vemurafenib during pregnancy
Show others...
2013 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, Vol. 31, no 11, p. e192-e193Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-328673 (URN)10.1200/JCO.2012.45.2870 (DOI)23401457 (PubMedID)
Available from: 2017-08-29 Created: 2017-08-29 Last updated: 2017-10-15Bibliographically approved
Organisations

Search in DiVA

Show all publications