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

Publication ,  Journal Article
Courrèges, MC; Benencia, F; Conejo-García, JR; Zhang, L; Coukos, G
Published in: Cancer Gene Ther
February 2006

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.

Duke Scholars

Published In

Cancer Gene Ther

DOI

ISSN

0929-1903

Publication Date

February 2006

Volume

13

Issue

2

Start / End Page

182 / 193

Location

England

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Vaccines, Synthetic
  • T-Lymphocytes, Cytotoxic
  • Simplexvirus
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
 

Citation

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MLA
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Courrèges, M. C., Benencia, F., Conejo-García, J. R., Zhang, L., & Coukos, G. (2006). Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines. Cancer Gene Ther, 13(2), 182–193. https://doi.org/10.1038/sj.cgt.7700888
Courrèges, M. C., F. Benencia, J. R. Conejo-García, L. Zhang, and G. Coukos. “Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines.Cancer Gene Ther 13, no. 2 (February 2006): 182–93. https://doi.org/10.1038/sj.cgt.7700888.
Courrèges MC, Benencia F, Conejo-García JR, Zhang L, Coukos G. Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines. Cancer Gene Ther. 2006 Feb;13(2):182–93.
Courrèges, M. C., et al. “Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines.Cancer Gene Ther, vol. 13, no. 2, Feb. 2006, pp. 182–93. Pubmed, doi:10.1038/sj.cgt.7700888.
Courrèges MC, Benencia F, Conejo-García JR, Zhang L, Coukos G. Preparation of apoptotic tumor cells with replication-incompetent HSV augments the efficacy of dendritic cell vaccines. Cancer Gene Ther. 2006 Feb;13(2):182–193.

Published In

Cancer Gene Ther

DOI

ISSN

0929-1903

Publication Date

February 2006

Volume

13

Issue

2

Start / End Page

182 / 193

Location

England

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Vaccines, Synthetic
  • T-Lymphocytes, Cytotoxic
  • Simplexvirus
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice