Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines.

Details

Serval ID
serval:BIB_1CF668A02CB6
Type
Article: article from journal or magazin.
Collection
Publications
Title
Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines.
Journal
Cancer Gene Therapy
Author(s)
Courrèges M.C., Benencia F., Conejo-García J.R., Zhang L., Coukos G.
ISSN
0929-1903 (Print)
ISSN-L
0929-1903
Publication state
Published
Issued date
2006
Volume
13
Number
2
Pages
182-193
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
The use of dendritic cells (DCs) loaded with apoptotic tumor cells is an attractive approach to tumor vaccination in the absence of well-characterized tumor antigens. Apoptotic tumor cells are a convenient source of polyvalent tumor antigen, but may induce only weak immunization. We tested the role of replication-incompetent recombinant herpes simplex virus (HSV) d106 lacking all immediate early genes except ICP0 in the generation of apoptotic cells for tumor vaccination, using ID8-VEGF, a syngeneic mouse model of ovarian carcinoma expressing high levels of VEGF, and TC-1, a human papillomavirus (HPV) 16 E6- and E7-transformed adenocarcinoma. HSVd106 killed tumor cells by apoptosis. Tumor cells infected by HSVd106 were engulfed more avidly by immature DCs, and induced DC maturation more efficiently than tumor cells killed by ultraviolet B (UVB) radiation. HSVd106 infection induced stronger upregulation of heat shock protein (Hsp) 70 and glucose-related protein (GRP) 94 than UVB in cells undergoing apoptosis. Immunization of mice with DCs loaded with HSVd106-killed cells elicited stronger antitumor T-cell response, including tumor-reactive interferon-gamma-secreting and cytotoxic T cells, and resulted in significantly stronger delay in tumor growth than immunization with DCs loaded with UVB-killed tumor cells. Moreover, in the TC-1 model, a protective effect of vaccination (40% tumor free animals) was observed only after immunization with DCs loaded with HSVd106-killed cells. Thus, the use of replication-incompetent HSV strains lacking immediate early genes except ICP0 offers possible advantages in the preparation of whole tumor cell antigen for DC-based tumor vaccination.
Keywords
Animals, Apoptosis/immunology, Carcinoma/immunology, Carcinoma/prevention & control, Chemotaxis/immunology, Dendritic Cells/immunology, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Gene Expression Regulation, Neoplastic/immunology, Genetic Vectors/genetics, HSP70 Heat-Shock Proteins/metabolism, Immunohistochemistry, Immunotherapy, Active/methods, Membrane Proteins/metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neoplasm Proteins/immunology, Ovarian Neoplasms/immunology, Ovarian Neoplasms/prevention & control, Simplexvirus, T-Lymphocytes, Cytotoxic/immunology, Vaccines, Synthetic/therapeutic use, Vascular Endothelial Growth Factor A/immunology
Pubmed
Web of science
Open Access
Yes
Create date
14/10/2014 11:43
Last modification date
20/08/2019 12:53
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