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Intratumoral gene delivery of anti-cathepsin L single-chain variable fragment by lentiviral vector inhibits tumor progression induced by human melanoma cells

Abstract : We previously demonstrated that the switch from non- to highly tumorigenic phenotype of human melanoma cells is directly related to procathepsin L secretion, which increased cell resistance to complement-mediated cell lysis. Involvement of procathepsin L secretion in tumor growth was clearly demonstrated by three different strategies: (1) inhibition of secreted procathepsin L activity; (2) increase of procathepsin L secretion; and (3) inhibition of procathepsin L secretion. This latter strategy was triggered by intracellular expression of anti-human cathepsin L single-chain variable fragment (ScFv). These previous experiments were performed by processing melanoma cells before their injection into nude mice. We herein designed a new lentiviral vector in which this anti-cathepsin L ScFv was cloned. This lentiviral vector was optimized to allow the highest intracellular expression of anti-cathepsin L ScFv in transduced melanoma cells. In these transduced cells, procathepsin L secretion was strongly inhibited. In addition, injection of this anti-cathepsin L ScFv lentiviral vector into tumors already induced in nude mice inhibited tumor growth and associated angiogenesis. This is the first report to demonstrate that targeting procathepsin L secretion with anti-cathepsin L ScFv lentiviral construct constitutes a new gene therapy in the challenge to inhibit the growth of tumors induced by human melanoma cells.
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https://www.hal.inserm.fr/inserm-03738136
Contributor : Didier Jean Connect in order to contact the contributor
Submitted on : Monday, July 25, 2022 - 5:26:15 PM
Last modification on : Wednesday, July 27, 2022 - 3:07:48 AM

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R Frade, N Rousselet, Didier Jean. Intratumoral gene delivery of anti-cathepsin L single-chain variable fragment by lentiviral vector inhibits tumor progression induced by human melanoma cells. Cancer Gene Therapy, Nature Publishing Group, 2008, 15 (9), pp.591-604. ⟨10.1038/cgt.2008.51⟩. ⟨inserm-03738136⟩

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