|Title:||Comparison of HPV DNA vaccines employing intracellular targeting strategies||Authors:||Kim J.W.
|Keywords:||DNA vaccines; E7; Human papillomavirus (HPV); Immunotherapy||Issue Date:||2004||Journal Volume:||11||Journal Issue:||12||Start page/Pages:||1011-1018||Source:||Gene Therapy||Abstract:||
Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. In the context of DNA vaccines, we previously used the gene gun approach to test several intracellular targeting strategies that are able to route a model antigen, such as the human papillomavirus type-16 (HPV-16) E7, to desired subcellular compartments in order to enhance antigen processing and presentation to T cells. These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat-shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain (dll) of Pseudomonas aeruginosa exotoxin A (ETA). Vaccination with DNA vaccines encoding E7 antigen linked to any of these molecules all led to a significant enhancement of E7-specific CD8+ T-cell immune responses and strong antitumor effects against an E7-expressing tumor, TC-1. However, we were interested in identifying the most potent DNA vaccine for our future clinical trials. Thus, we performed a series of experiments to directly compare the potency of the various DNA vaccines. Among the DNA vaccines we tested, we found that vaccination with pcDNA3-CRT/E7 generated the highest number of E7-specific CD8+ T cells and potent long-term protection and treatment effects against E7-expressing tumors in mice. Interestingly, we observed that pcDNA3-CRT/E7 is also capable of protecting against an E7-expressing tumor with downregulated MHC class I expression, a common feature associated with most HPV-associated cervical cancers. Our data suggest that the DNA vaccine linking CRT to E7 (CRT/E7) may be a suitable candidate for human trials for the control of HPV infections and HPV-associated lesions. ? 2004 Nature Publishing Group All rights reserved.
|ISSN:||0969-7128||DOI:||10.1038/sj.gt.3302252||SDG/Keyword:||CD8 antigen; complementary DNA; DNA vaccine; gamma interferon; major histocompatibility antigen class 1; plasmid DNA; virus antigen; animal cell; animal experiment; animal model; antigen expression; antineoplastic activity; article; controlled study; data analysis; disease association; down regulation; drug potency; drug targeting; experimentation; female; gene gun; lymphocyte count; mouse; nonhuman; priority journal; protection; protein expression; T lymphocyte; tumor; uterine cervix cancer; vaccination; virus infection; Wart virus; Animals; Biolistics; Calreticulin; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Female; Gene Targeting; Gene Therapy; Histocompatibility Antigens Class I; Humans; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus Infections; Recombinant Proteins; Skin; Vaccines, DNA; Human papillomavirus; Human papillomavirus type 16; Human papillomavirus types; Mycobacterium; Mycobacterium tuberculosis; Papillomavirus; Pseudomonas; Pseudomonas aeruginosa
|Appears in Collections:||臨床醫學研究所|
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