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

Direct link
Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
Show others and affiliations
2016 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 8, 872-880 p.Article 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.

Place, publisher, year, edition, pages
2016. Vol. 114, no 8, 872-880 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-295735DOI: 10.1038/bjc.2016.42ISI: 000374129200004PubMedID: 27031851OAI: oai:DiVA.org:uu-295735DiVA: diva2:934579
Funder
Swedish Cancer Society
Available from: 2016-06-09 Created: 2016-06-09 Last updated: 2016-08-08Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Loskog, AngelicaMaleka, AglaiaMangsbo, SaraSvensson, EmmaLundberg, ChristinaNilsson, AndersKrause, JohanSundin, AndersAhlström, HåkanTötterman, Thomas HUllenhag, Gustav
By organisation
Clinical ImmunologyExperimental and Clinical OncologyEvolution and Developmental BiologyRadiology
In the same journal
British Journal of Cancer
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 105 hits
ReferencesLink to record
Permanent link

Direct link