Gene gun-mediated dna vaccination induces antitumor immunity against human papillomavirus type 16 e7-expressing murine tumor metastases in the liver and lungs

ABSTRACT DNA vaccination has emerged as an attractive approach for tumor immunotherapy. The aim of this study was to evaluate the potency of DNA vaccines in preventing and treating the liver

and lung metastases of a human papillomavirus-16 (HPV-16) E7-expressing murine tumor (TC-1). We used the gene gun method to vaccinate C57BL/6 mice intradermally with DNA vaccines containing

the HPV-16 E7 gene, the E7 gene linked to the sorting signals of the lysosome-associated membrane protein-1 (Sig/E7/ LAMP-1), or the ‘empty’ plasmid vector. The in vivo antitumor immunity

was analyzed in both tumor prevention and tumor regression experiments. In addition, cytotoxic T lymphocyte (CTL) assays, enzyme-linked immunospot assay and enzyme-linked immunoabsorbent

assay were used to assess the E7-specific T cell-mediated and humoral immunity. Mice vaccinated with Sig/E7/LAMP-1 DNA generated the strongest E7-specific CTL activities, the highest numbers

of E7-specific CD8+ cell precursors and the highest titers of E7-specific antibodies. While both E7 DNA and Sig/E7/LAMP-1 DNA generated potent antitumor immunity in the liver and lung

metastases models, the Sig/E7/LAMP-1 DNA was more potent under stringent conditions. DNA vaccination with E7-expressing plasmids was effective in controlling liver and lung metastases of an

E7-expressing murine tumor. Our data suggest that antigen-specific DNA vaccination can potentially be applied to control liver and lung metastases of tumors with defined tumor-specific

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support SIMILAR CONTENT BEING VIEWED BY OTHERS COMBINATION IMMUNOTHERAPY WITH TWO ATTENUATED _LISTERIA_ STRAINS CARRYING SHUFFLED HPV-16 E6E7 PROTEIN CAUSES TUMOR REGRESSION IN A MOUSE

TUMOR MODEL Article Open access 28 June 2021 CHIMERIC ADENOVIRAL (AD5.F35) AND LISTERIA VECTOR PRIME-BOOST IMMUNIZATION IS SAFE AND EFFECTIVE FOR CANCER IMMUNOTHERAPY Article Open access 23

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like to thank Drs Tian-Li Wang, Chien-Fu Hung and Robert J Kurman for helpful discussions. We would also like to thank Haiyan Chen for superb technical help and Morris Ling for preparation

of the manuscript. This work was supported by NIH 5 po1 34582-01, U19 CA72108-02, RO1 CA72631-01 and the Richard W TeLinde endowment. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department

of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA C-H Chen, D M Pardoll & T-C Wu * Department of Internal Medicine, National Taiwan University Hospital,

National Taiwan University, Taipei, Taiwan C-H Chen * Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA H Ji & T-C Wu * Department of Surgery, The

Johns Hopkins Medical Institutions, Baltimore, Maryland, USA K W Suh & M A Choti * Department of Surgery, School of Medicine, Ajou University, South Korea K W Suh * Department of

Obstetrics and Gynecology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA T-C Wu * Department of Molecular Microbiology and Immunology, The Johns Hopkins Medical

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You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Chen, CH., Ji, H., Suh, K. _et al._ Gene

gun-mediated DNA vaccination induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the liver and lungs. _Gene Ther_ 6, 1972–1981 (1999).

https://doi.org/10.1038/sj.gt.3301067 Download citation * Received: 28 June 1999 * Accepted: 31 August 1999 * Published: 05 January 2000 * Issue Date: 01 December 1999 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * DNA vaccine * metastasis * human papillomaviruses *

LAMP-1 * antitumor * E7