PMID- 14670335
OWN - NLM
STAT- MEDLINE
DCOM- 20040319
LR  - 20220310
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 22
IP  - 3-4
DP  - 2004 Jan 2
TI  - Antitumor efficacy of Venezuelan equine encephalitis virus replicon particles 
      encoding mutated HPV16 E6 and E7 genes.
PG  - 520-7
AB  - An effective vaccine for treating human papillomavirus (HPV)-associated 
      malignancies such as cervical cancer should elicit strong T cell-mediated 
      immunity (CMI) against the E6 and/or E7 proteins necessary for the malignant 
      state. We have developed Venezuelan equine encephalitis (VEE) virus replicon 
      particle (VRP) vaccines encoding the HPV16 E6 and E7 genes and tested their 
      immunogenicity and antitumor efficacy. The E6 and E7 genes were fused to create 
      one open reading frame and mutated at four or at five amino acid positions to 
      inactivate their oncogenic potential. VRP encoding mutant or wild type E6 and E7 
      proteins elicited comparable cytotoxic T lymphocyte (CTL) responses to an 
      immunodominant E7(49-57) epitope and generated comparable antitumor responses in 
      several HPV16 E6(+)E7(+) tumor challenge models: protection from either C3 or 
      TC-1 tumor challenge was observed in 100% of VRP-vaccinated mice. Eradication of 
      C3 tumors was observed in approximately 90% of mice following therapeutic VRP 
      vaccination. Eradication of HLF16 tumors lacking the E7(49-57) epitope was 
      observed in 90% of human leukocyte antigen (HLA)-A(*)0201 transgenic mice 
      following therapeutic VRP vaccination. Finally, the predicted inactivation of E6 
      and E7 oncogenic potential was confirmed by demonstrating normal levels of both 
      p53 and retinoblastoma proteins in human mammary epithelial cells (MEC) infected 
      with VRP expressing mutant E6 and E7 genes. These promising results support the 
      continued development of mutant E6 and E7 VRP as safe and effective candidates 
      for clinical evaluation against HPV-associated disease.
FAU - Cassetti, M Cristina
AU  - Cassetti MC
AD  - Wyeth Vaccines Research, Pearl River, NY 10965, USA.
FAU - McElhiney, Sue P
AU  - McElhiney SP
FAU - Shahabi, Vafa
AU  - Shahabi V
FAU - Pullen, Jeffrey K
AU  - Pullen JK
FAU - Le Poole, I Caroline
AU  - Le Poole IC
FAU - Eiben, Gretchen L
AU  - Eiben GL
FAU - Smith, Larry R
AU  - Smith LR
FAU - Kast, W Martin
AU  - Kast WM
LA  - eng
GR  - P01 CA97296/CA/NCI NIH HHS/United States
GR  - R01 CA74397/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Encephalitis Virus, Venezuelan Equine/*immunology
MH  - Female
MH  - Genes, Viral/*immunology
MH  - Genes, p53/genetics
MH  - Immunization
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutagenesis/genetics
MH  - Neoplasm Transplantation
MH  - Oncogene Proteins, Viral/*genetics/*immunology
MH  - Papilloma/*prevention & control/*virology
MH  - Papillomaviridae/*immunology
MH  - Papillomavirus E7 Proteins
MH  - Phenotype
MH  - Replicon/*immunology
MH  - *Repressor Proteins
EDAT- 2003/12/13 05:00
MHDA- 2004/03/20 05:00
CRDT- 2003/12/13 05:00
PHST- 2003/12/13 05:00 [pubmed]
PHST- 2004/03/20 05:00 [medline]
PHST- 2003/12/13 05:00 [entrez]
AID - S0264410X03005802 [pii]
AID - 10.1016/j.vaccine.2003.07.003 [doi]
PST - ppublish
SO  - Vaccine. 2004 Jan 2;22(3-4):520-7. doi: 10.1016/j.vaccine.2003.07.003.