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Br J Cancer. 2016 Apr 12;114(8):872-80. doi: 10.1038/bjc.2016.42. Epub 2016 Mar 31.

Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients.

Author information

1
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Dag Hammarskjoldsvag 20, 75185 Uppsala, Sweden.
2
Department of Oncology, Uppsala University Hospital, 75185 Uppsala, Sweden.
3
Division of Radiology, Uppsala University Hospital, 75185 Uppsala, Sweden.
4
Department of Pathology and Cytology, Uppsala University Hospital, 75185 Uppsala, Sweden.
5
Department of Surgical Sciences, Uppsala University, 75185 Uppsala, Sweden.

Abstract

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.

PMID:
27031851
PMCID:
PMC4984796
DOI:
10.1038/bjc.2016.42
[Indexed for MEDLINE]
Free PMC Article

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