PMID- 11034088
OWN - NLM
STAT- MEDLINE
DCOM- 20001027
LR  - 20171116
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 60
IP  - 19
DP  - 2000 Oct 1
TI  - Adenoviral vectors targeted to CD40 enhance the efficacy of dendritic cell-based 
      vaccination against human papillomavirus 16-induced tumor cells in a murine 
      model.
PG  - 5456-63
AB  - Dendritic cells (DCs) represent a unique junction from which to initiate 
      antigen-specific immunity. One of the most challenging obstacles for DC-based 
      immunotherapy has been the means by which to convey tumor antigen-encoding genes 
      to DCs. In this study, we show that adenoviral (or adenovirus, Ad) vectors 
      targeted to CD40 by means of bispecific antibodies can enhance gene transfer to 
      murine DCs. Moreover, we illustrate that this vector initiates phenotypic changes 
      characteristic of DC maturation. To explore the in vivo potential of this 
      strategy, we coupled this targeting approach with an Ad vector carrying the gene 
      for a tumor antigen. In particular, the human papillomavirus (HPV) E7 antigen 
      represents an attractive target for antigen-specific immunity of cervical cancer. 
      Relative to DCs infected by untargeted Ad, DCs infected by AdE7 targeted to the 
      receptor CD40 enhanced protection against HPV-16-induced tumor cells in a murine 
      model. We have further established that this protection was both antigen specific 
      and CD8+ T-cell dependent. Illustrating that Ad-modified DCs may be used in 
      repeated vaccination, we report that preimmunization of animals with Ad infected 
      DCs prior to E7 vaccination only moderately reduced vaccine efficacy. Finally, we 
      have observed that CD40-targeted AdE7 can initiate partial therapeutic immunity 
      in mice bearing established tumors. These findings suggest that gene-based 
      vaccination of DCs with tumor antigens can elicit productive antitumoral immunity 
      and that enhancements in gene transfer efficacy and/or DC maturation may 
      facilitate this process.
FAU - Tillman, B W
AU  - Tillman BW
AD  - Department of Medicine,Gene Therapy Center, University of Alabama at Birminghanm, 
      35294, USA.
FAU - Hayes, T L
AU  - Hayes TL
FAU - DeGruijl, T D
AU  - DeGruijl TD
FAU - Douglas, J T
AU  - Douglas JT
FAU - Curiel, D T
AU  - Curiel DT
LA  - eng
GR  - R01CA68245/CA/NCI NIH HHS/United States
GR  - R01CA74242/CA/NCI NIH HHS/United States
GR  - R01CA86881-01/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CD40 Antigens)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - CD40 Antigens/genetics/*immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/genetics/*immunology
MH  - Dendritic Cells/*immunology
MH  - Epitopes/immunology
MH  - Gene Targeting/*methods
MH  - Gene Transfer Techniques
MH  - Genetic Vectors
MH  - Humans
MH  - Immunotherapy, Active
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasms, Experimental/*immunology/therapy/virology
MH  - Oncogene Proteins, Viral/biosynthesis/genetics/*immunology
MH  - *Papillomaviridae/genetics/immunology
MH  - Papillomavirus E7 Proteins
MH  - Phenotype
EDAT- 2000/10/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/18 11:00
PHST- 2000/10/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/18 11:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2000 Oct 1;60(19):5456-63.