Intranodal Immunization With a Vaccinia Virus Encoding Multiple Antigenic Epitopes and Costimulatory Molecules in Metastatic Melanoma

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) vaccin...

Full description

Saved in:
Bibliographic Details
Published in:Molecular therapy 2010-03, Vol.18 (3), p.651-659
Main Authors: Adamina, Michel, Rosenthal, Rachel, Weber, Walter P, Frey, Daniel M, Viehl, Carsten T, Bolli, Martin, Huegli, Rolf W, Jacob, Augustinus L, Heberer, Michael, Oertli, Daniel, Marti, Walter, Spagnoli, Giulio C, Zajac, Paul
Format: Article
Language:English
Subjects:
Adenoviruses
Adult
Aged
Aged, 80 and over
Antigens
Antigens, Neoplasm - metabolism
Cancer
Cancer Vaccines - therapeutic use
Cytotoxicity
Disease Progression
Epitopes - chemistry
Female
Genes
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Granulocytes
Humans
Immunization - methods
Immunotherapy
Injections
Lymph Nodes - pathology
Male
Melanoma
Melanoma - pathology
Melanoma - therapy
Metastasis
Middle Aged
Neoplasm Metastasis
Original
Patients
Peptides
Reagents
T-Lymphocytes, Cytotoxic - metabolism
Tumors
Vaccinia virus - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 gp100280–288, Melan-A/MART-127–35 and tyrosinase1–9 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.
ISSN:1525-0016
1525-0024
DOI:10.1038/mt.2009.275