Stable Antibody Expression at Therapeutic Levels Using The 2A Peptides  

Oleh:

Jianmin Fang ; Jing-jing Qian ; Saili, Yi ; Harding, Thomas C. ; Guang, Huan Tu ; VanRoey, Melinda ; Jooss, Karin

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 23 no. 5 (Mei 2005), page 584-590.
Topik: THERAPEUTICS; antibody; therapeutic; peptide

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.3 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Therapeutic monoclonal antibodies (mAbs) are currently being developed for the treatment of cancer and other disease. Despite clinical success, widespread application of mAv therapies may be limited by manufacturing capabilities. In this paper, we describe a mAb delivery system that allows continuous production of a full length antibody at high concentrations in vivo after gene transfer. The mAb is expressed from a single open reading frame by linking the heavy and light chains with a 2A self processing peptide derived from the foot and mouth disease virus. Using this expression system, we generated a recombinant adeno-associated virus vector encoding the VEGFR2-neutralizing mAb DC101 (rAAV8-DC101). A single dose of rAAV8-DC101 resulted in long term expression of 1,000 ug/ml of DC101 in mice, demonstrating significant anti-tumor efficacy. This report describes the first feasible gene therapy approach for stable delivery of mAbs at therapeutic levels, which may serve as an attractive alternative to direct injection of mAbs.

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