Title: "Active" Cancer Immunotherapy by Anti-Met Antibody Gene Transfer
Authors: Vigna, Elisa ×
Pacchiana, Giovanni
Mazzone, Max
Chiriaco, Cristina
Fontani, Lara
Basilico, Cristina
Pennacchietti, Selma
Comoglio, Paolo M #
Issue Date: Nov-2008
Publisher: Amer assoc cancer research
Series Title: Cancer research vol:68 issue:22 pages:9176-9183
Abstract: Gene therapy provides a still poorly explored opportunity to treat cancer by "active" immunotherapy as it enables the transfer of genes encoding antibodies directed against specific oncogenic proteins. By a bidirectional lentiviral vector, we transferred the cDNA encoding the heavy and light chains of a monoclonal anti-Met antibody (DN-30) to epithelial cancer cells. In vitro, the transduced cells synthesized and secreted correctly assembled antibodies with the expected high affinity, inducing down-regulation of the Met receptor and strong inhibition of the invasive growth response. The inhibitory activity resulted (a) from the interference of the antibody with the Met receptor intracellular processing ("cell autonomous activity," in cis) and (b) from the antibody-induced cleavage of Met expressed at the cell surface ("bystander effect;" in trans). The monoclonal antibody gene transferred into live animals by systemic administration or by local intratumor delivery resulted in substantial inhibition of tumor growth. These data provide proof of concept both for targeting the Met receptor and for a gene transfer-based immunotherapy strategy. [Cancer Res 2008;68(22):9176-83]
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Tumor Inflammation and Angiogenesis (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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