Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Aug;60(8):1147-51.
doi: 10.1007/s00262-011-1042-2. Epub 2011 Jun 5.

DNA fusion vaccines enter the clinic

Freda K Stevenson  1 , Ann Mander, Lindsey Chudley, Christian H Ottensmeier
Affiliations
Review

DNA fusion vaccines enter the clinic

Freda K Stevenson et al. Cancer Immunol Immunother. 2011 Aug.

Abstract

Induction of effective immune attack on cancer cells in patients requires conversion of weak tumor antigens into strong immunogens. Our strategy employs genetic technology to create DNA vaccines containing tumor antigen sequences fused to microbial genes. The fused microbial protein engages local CD4+ T cells to provide help for anti-tumor immunity, and to reverse potential regulation. In this review, we focus on induction of CD8+ T cells able to kill target tumor cells. The DNA vaccines incorporate tumor-derived peptide sequences fused to an engineered domain of tetanus toxin. In multiple models, this design induces strong CD8+ T-cell responses, able to suppress tumor growth. For clinical relevance, we have used "humanized" mice expressing HLA-A2, successfully inducing cytolytic T-cell responses against a range of candidate human peptides. To overcome physical restriction in translating to patients, we have used electroporation. Clinical trials of patients with cancer are showing induction of responses, with preliminary indications of suppression of tumor growth and evidence for clinically manageable concomitant autoimmunity.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
The p. DOM-epitope plasmid design incorporates three components: the backbone of bacterial DNA, the tumor-derived target peptide (or protein) sequence, and microbial sequences to activate T-cell help, derived from Tetanus Toxin or from plant viral coat proteins
Fig. 2
Fig. 2
The design of the p.DOM-epitope vaccines aimed to induce anti-tumor CD8+ T cells. The Fragment C of tetanus toxin has been engineered to include only the N-terminal domain (DOM 1) which contains the promiscuous p30 epitope able to induce T-cell help. The second domain (DOM 2) that contains potentially competitive MHC Class I (HLA-A2)-binding peptides has been removed. The tumor-derived target peptide sequence is then placed at the C-terminus of DOM 1
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol. 2002;20:709–760. doi: 10.1146/annurev.immunol.20.100301.064842. - DOI - PubMed
    1. Spies B, Hochrein H, Vabulas M, Huster K, Busch DH, Schmitz F, Heit A, Wagner H. Vaccination with plasmid DNA activates dendritic cells via toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice. J Immunol. 2003;171(11):5908–5912. - PubMed
    1. Wang Z, Choi MK, Ban T, Yanai H, Negishi H, Lu Y, Tamura T, Takaoka A, Nishikura K, Taniguchi T. Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules. Proc Natl Acad Sci USA. 2008;105(14):5477–5482. doi: 10.1073/pnas.0801295105. - DOI - PMC - PubMed
    1. Burckstummer T, Baumann C, Bluml S, Dixit E, Durnberger G, Jahn H, Planyavsky M, Bilban M, Colinge J, Bennett KL, Superti-Furga G. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol. 2009;10(3):266–272. doi: 10.1038/ni.1702. - DOI - PubMed
    1. Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999;50(3–4):213–219. doi: 10.1007/s002510050595. - DOI - PubMed

Publication types

MeSH terms