Lentiviral vector-mediated tyro sinase-related protein 2 gene transfer to dendritic cells for the therapy of melanoma

Metharom, P, Ellem, KAO, Schmidt, C and Wei, MQ (2001) Lentiviral vector-mediated tyro sinase-related protein 2 gene transfer to dendritic cells for the therapy of melanoma. Human Gene Therapy, 12 18: 2203-2213. doi:10.1089/10430340152710540


Author Metharom, P
Ellem, KAO
Schmidt, C
Wei, MQ
Title Lentiviral vector-mediated tyro sinase-related protein 2 gene transfer to dendritic cells for the therapy of melanoma
Journal name Human Gene Therapy   Check publisher's open access policy
ISSN 1043-0342
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1089/10430340152710540
Open Access Status Not Open Access
Volume 12
Issue 18
Start page 2203
End page 2213
Total pages 11
Language eng
Abstract 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.
Keyword Biotechnology & Applied Microbiology
Genetics & Heredity
Medicine, Research & Experimental
Cytotoxic T-lymphocytes
Immune-response
Dopachrome Tautomerase
Tumor-antigens
B16 Melanoma
Bone-marrow
Cord-blood
In-vitro
Tyrosinase
Cd4(+)
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Mon, 13 Aug 2007, 22:44:03 EST