PMID- 15085173
OWN - NLM
STAT- MEDLINE
DCOM- 20040809
LR  - 20121115
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 11
IP  - 11
DP  - 2004 Jun
TI  - Secretory heat-shock protein as a dendritic cell-targeting molecule: a new 
      strategy to enhance the potency of genetic vaccines.
PG  - 924-32
AB  - DNA vaccines are an appealing strategy for inducing cytotoxic T-lymphocyte and 
      antibody responses against tumor cells as well as infectious agents. Dendritic 
      cells (DCs) play a critical role in inducing immune responses, but their 
      potential is not fully utilized in the DNA vaccine setting since they take up 
      only a minor fraction of the injected DNA. Here we describe a novel DNA 
      vaccination strategy based on the targeting of a modified tumor-associated 
      antigen, the human papilloma virus (HPV) type 16 E7 protein, to DCs by a 
      heat-shock protein (HSP) to enhance antigen presentation and immune responses. 
      Specifically, a chimerical HPV-E7 and HSP70 fusion gene preceded with a leader 
      sequence was constructed. When mice were immunized with this construct, the DNA 
      is taken up by various types of cells, which then produce and secrete an 
      HPV-E7-HSP70 fusion protein that is targeted to DCs by the HSP70 portion of the 
      chimerical molecule for antigen presentation. In studies to test the efficacy of 
      this strategy, we demonstrated that DNA vaccination with this secretory 
      HPV-E7-HSP70 construct strongly enhanced an antigen-specific CD8+ T-cell response 
      as well as a specific B-cell response in mice. Furthermore, this immunization 
      approach not only protected mice against lethal challenge with an HPV 
      E7-expressing tumor line (TC-1), but also showed a therapeutic effect against 
      established tumors. The results of this study indicate that secretory HSPs can be 
      broadly used to target tumor-associated antigens to DCs to enhance 
      antigen-specific immune responses.
FAU - Hauser, H
AU  - Hauser H
AD  - Department of Molecular and Human Genetics, Center for Cell and Gene Therapy, 
      Baylor College of Medicine, Houston, TX 77030, USA.
FAU - Shen, L
AU  - Shen L
FAU - Gu, Q-L
AU  - Gu QL
FAU - Krueger, S
AU  - Krueger S
FAU - Chen, S-Y
AU  - Chen SY
LA  - eng
GR  - 48711/PHS HHS/United States
GR  - R01 AI48480/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antigens, Viral, Tumor)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Vaccines, DNA)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - Animals
MH  - Antibodies, Viral/blood
MH  - Antigen Presentation
MH  - Antigens, Viral, Tumor/*genetics
MH  - Cancer Vaccines
MH  - Cell Line
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Genetic Therapy/*methods
MH  - Heat-Shock Proteins/*genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasm Transplantation
MH  - Neoplasms/therapy
MH  - Oncogene Proteins, Viral/*genetics/immunology
MH  - Papillomavirus E7 Proteins
MH  - Vaccines, DNA/*administration & dosage
EDAT- 2004/04/16 05:00
MHDA- 2004/08/10 05:00
CRDT- 2004/04/16 05:00
PHST- 2004/04/16 05:00 [pubmed]
PHST- 2004/08/10 05:00 [medline]
PHST- 2004/04/16 05:00 [entrez]
AID - 3302160 [pii]
AID - 10.1038/sj.gt.3302160 [doi]
PST - ppublish
SO  - Gene Ther. 2004 Jun;11(11):924-32. doi: 10.1038/sj.gt.3302160.