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Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients.
- Source :
- Journal of Translational Medicine; 4/20/2017, Vol. 15, p1-11, 11p
- Publication Year :
- 2017
-
Abstract
- <bold>Background and Aims: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>AdCD40L intratumoral injection induced desirable systemic immune effects that correlated to prolonged survival. Further studies using CD40 stimulation in malignant melanoma are warranted. Trial registration The 002:CD40L trial "Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors" (clinicalTrials.gov identifier: NCT01455259) was registered at September 2011. [ABSTRACT FROM AUTHOR]
- Subjects :
- ADENOVIRUSES
ADENOVIRUS diseases
GENETIC transformation
T cell receptors
DEATH receptors
MELANOMA
IMMUNOTHERAPY
GENETICS
PATIENTS
MELANOMA treatment
METABOLISM in viruses
ANTIGENS
BIOCHEMISTRY
CELL receptors
CLINICAL trials
COMPARATIVE studies
GENETIC techniques
GLYCOPROTEINS
HEMATOPOIETIC growth factors
PHENOMENOLOGY
RESEARCH methodology
MEDICAL cooperation
RESEARCH
SURVIVAL analysis (Biometry)
T cells
PROTEOMICS
EVALUATION research
LYMPHOCYTE count
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 15
- Database :
- Complementary Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 122648952
- Full Text :
- https://doi.org/10.1186/s12967-017-1182-z