Abstract
BackgroundPlant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a humanized monoclonal antibody (mAb), trastuzumab (Herceptin). A course of treatment, however, is expensive and requires repeated administrations of the mAb. Here we used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells.Methodology/Principal FindingsWe describe the cloning and expression of gene constructs in Nicotiana benthamiana plants using intron-optimized Tobacco mosaic virus- and Potato virus X-based vectors encoding, respectively, the heavy and light chains of trastuzumab. Full-size antibodies extracted and purified from plant tissues were tested for functionality and specificity by (i) binding to HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, in fluorescence-activated cell sorting assay and (ii) testing the in vitro and in vivo inhibition of HER-2-expressing cancer cell proliferation. We show that plant-made trastuzumab (PMT) bound to the Her2/neu oncoprotein of SK-BR-3 cells and efficiently inhibited SK-BR-3 cell proliferation. Furthermore, mouse intraperitoneal PMT administration retarded the growth of xenografted tumors derived from human ovarian cancer SKOV3 Her2+ cells.Conclusions/SignificanceWe conclude that PMT is active in suppression of cell proliferation and tumor growth.
Highlights
There was a time when most medicinal compounds were extracted from plants, but plant molecular biology produces valuable recombinant pharmaceutical molecules, including enzymes, vaccines, and antibodies [1,2,3,4,5,6,7,8,9]
Human epidermal growth factor receptor 2 (HER2/neu) is an oncogene involved in abnormal cell growth in breast cancer and is a target for the humanised monoclonal antibody trastuzumab (Herceptin) [23], which was approved by the US Food and Drug Administration for the treatment of HER2/neu-overexpressing breast tumours
We used genes encoding both heavy and light chains of trastuzumab, cloned into 35S- and virus-based vectors and expressed in Nicotiana benthamiana leaves. We show that both vector systems result in high yield of full-size antibodies, plant-made trastuzumab (PMT), which recognizes HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, and active in suppression of cell proliferation in vitro
Summary
There was a time when most medicinal compounds were extracted from plants, but plant molecular biology produces valuable recombinant pharmaceutical molecules, including enzymes, vaccines, and antibodies [1,2,3,4,5,6,7,8,9]. Such ‘‘molecular farming’’ has many economic and qualitative benefits, including reduced health risks from human and animal pathogen contamination and comparatively high yields. We used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells
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