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Intranodal immunization with a vaccinia virus encoding multiple antigenic epitopes and costimulatory molecules in metastatic melanoma

Adamina, Michel and Rosenthal, Rachel and Weber, Walter P. and Frey, Daniel M. and Viehl, Carsten T. and Bolli, Martin and Huegli, Rolf W. and Jacob, Augustinus L. and Heberer, Michael and Oertli, Daniel and Marti, Walter and Spagnoli, Giulio C. and Zajac, Paul. (2010) Intranodal immunization with a vaccinia virus encoding multiple antigenic epitopes and costimulatory molecules in metastatic melanoma. Molecular therapy, Vol. 18, H. 3. pp. 651-659.

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Official URL: http://edoc.unibas.ch/dok/A6006157

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Abstract

Recombinant vaccinia virus (rVV) encoding tumor-associated antigens (TAAs) and adhesion or costimulatory molecules may represent important immunogenic reagents for cancer immunotherapy. Recently, intranodal (IN) antigen administration was suggested to be more immunogenic than intradermal (ID) vaccination. However, IN rVV administration has not been attempted so far. We used a rVV encoding gp100(280-288), Melan-A/MART-1(27-35) and tyrosinase(1-9) HLA-A0201 restricted epitopes and CD80 and CD86 costimulatory molecules in stage III and IV melanoma patients in a phase 1/2 trial. Of 15 patients initiating treatment, including two cycles of IN immunization, each comprising one rVV administration and three recall injections of the corresponding peptides, accompanied by subcutaneous granulocyte macrophage-colony stimulating factor supplementation, five withdrew due to progressing disease. Of 10 remaining patients seven showed evidence of induction of cytotoxic T lymphocytes (CTLs) directed against at least one epitope under investigation, as detectable by limiting dilution analysis (LDA) of specific precursors and multimer staining. Adverse reactions were mild (National Cancer Institute (NCI) grade 1-2) and mainly represented by fever, skin rashes, and pruritus. These data indicate that IN administration of rVV encoding melanoma-associated epitopes and costimulatory molecules is safe and immunogenic.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe > Allgemein- und Viszeralchirurgie (Oertli)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe > Allgemein- und Viszeralchirurgie (Oertli)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Radiologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Radiologie USB
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Interventionelle Radiologie (Jacob)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Interventionelle Radiologie (Jacob)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Klinische Forschung in der Chirurgie (Rosenthal)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Klinische Forschung in der Chirurgie (Rosenthal)
UniBasel Contributors:Jacob, Augustinus Ludwig and Spagnoli, Giulio C. and Oertli, Daniel and Zajac, Paul and Bolli, Martin and Viehl, Carsten Thomas and Adamina, Michel and Hügli, Rolf and Weber, Walter P. and Rosenthal, Rachel
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature
ISSN:1525-0016
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:18 Dec 2015 09:32
Deposited On:08 Nov 2012 16:15

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