PMID- 11779404
OWN - NLM
STAT- MEDLINE
DCOM- 20020320
LR  - 20061115
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 12
IP  - 18
DP  - 2001 Dec 10
TI  - Lentiviral vector-mediated tyrosinase-related protein 2 gene transfer to 
      dendritic cells for the therapy of melanoma.
PG  - 2203-13
AB  - Dendritic cells (DCs) are the most potent professional antigen-presenting cells 
      (APCs), which play a vital role in primary immune responses. Introducing genes 
      into DCs will allow constitutive expression of the encoded proteins and thus 
      prolong the presentation of the antigens derived therefrom. In addition, multiple 
      and unidentified epitopes encoded by the entire tumor-associated antigen (TAA) 
      gene may enhance T cell activation. This study demonstrated that an HIV-1-based 
      lentiviral vector conferred efficient gene transfer to DCs. The transgene, murine 
      tyrosinase-related protein 2 (mTRP-2), encodes a clinically relevant 
      melanoma-associated antigen (MAA), which has been found to be a tumor rejection 
      antigen for B16 melanoma. The transfer and proper processing of mTRP-2 in DCs, in 
      terms of RNA transcription activity and protein expression, were verified by 
      RT-PCR and specific antibody, respectively. Administration of mTRP-2 
      gene-modified DCs (DC-HR' CmT2) to C57BL/6 mice evoked strong protection against 
      tumor challenge, for which the presence of CD4+ and CD8+ cells during both the 
      priming and challenge phase was essential. In a therapy model, our results showed 
      that four of seven mice with preestablished tumor remained tumor free for 80 days 
      after therapeutic vaccination. Given the results shown in this study, mTRP-2 gene 
      transfer to DCs provides a potential therapeutic strategy for the management of 
      melanoma, especially in the early stage of the disease.
FAU - Metharom, P
AU  - Metharom P
AD  - Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, 
      Queensland 4029, Australia.
FAU - Ellem, K A
AU  - Ellem KA
FAU - Schmidt, C
AU  - Schmidt C
FAU - Wei, M Q
AU  - Wei MQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Antigens, Neoplasm)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.3.12 (dopachrome isomerase)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/*genetics
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - *Dendritic Cells/immunology
MH  - Female
MH  - Gene Expression
MH  - Gene Transfer Techniques
MH  - *Genetic Vectors
MH  - *HIV-1
MH  - Humans
MH  - Immunotherapy/methods
MH  - Intramolecular Oxidoreductases/*genetics
MH  - Melanoma/*therapy
MH  - Mice
MH  - Mice, Inbred C57BL
EDAT- 2002/01/10 10:00
MHDA- 2002/03/21 10:01
CRDT- 2002/01/10 10:00
PHST- 2002/01/10 10:00 [pubmed]
PHST- 2002/03/21 10:01 [medline]
PHST- 2002/01/10 10:00 [entrez]
AID - 10.1089/10430340152710540 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2001 Dec 10;12(18):2203-13. doi: 10.1089/10430340152710540.