Plant-made trastuzumab (herceptin) inhibits HER2/Neu+ cell proliferation and retards tumor growth.
Plant-made trastuzumab (herceptin) inhibits HER2/Neu+ cell proliferation and retards tumor growth.
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DOI：
10.1371/journal.pone.0017541
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发表时间：
2011-03-03
期刊：
影响因子：
3.7
通讯作者：
Dorokhov YL
中科院分区：
文献类型：
--
作者：
Komarova TV;Kosorukov VS;Frolova OY;Petrunia IV;Skrypnik KA;Gleba YY;Dorokhov YL
植物生物技术为全球健康做出了宝贵的贡献，部分原因是它可以降低药品的成本。乳腺癌现在可以成功地治疗的人源化单克隆抗体（mAb），曲妥珠单抗（赫赛汀）。然而，治疗过程是昂贵的，并且需要重复施用mAb。在这里，我们使用了农杆菌介导的瞬时表达系统在植物细胞中产生曲妥珠单抗。我们描述了使用内含子优化的烟草花叶病毒和马铃薯X病毒为基础的载体，分别编码曲妥珠单抗的重链和轻链的基因构建体在本氏烟草植物中的克隆和表达。从植物组织中提取和纯化的全尺寸抗体通过以下测试功能性和特异性：（i）在荧光激活细胞分选测定中与人乳腺腺癌细胞系SK-BR-3表面上的HER 2/neu结合，和（ii）测试表达HER-2的癌细胞增殖的体外和体内抑制。我们发现，植物制造的曲妥珠单抗（PMT）结合到SK-BR-3细胞的Her 2/neu癌蛋白，并有效地抑制SK-BR-3细胞增殖。此外，小鼠腹膜内PMT给药延缓了来自人卵巢癌SKOV 3 Her 2+细胞的异种移植肿瘤的生长。我们的结论是，PMT是积极的抑制细胞增殖和肿瘤生长。
Plant 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. We 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. We conclude that PMT is active in suppression of cell proliferation and tumor growth.
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影响因子：
50.3
作者：
Junttila, Teemu T.;Akita, Robert W.;Sliwkowski, Mark X.
通讯作者：
Sliwkowski, Mark X.
DOI：
10.1073/pnas.0606631103
发表时间：
2006-10-03
影响因子：
11.1
作者：
Giritch, Anatoli;Marillonnet, Sylvestre;Gleba, Yuri
通讯作者：
Gleba, Yuri
影响因子：
64.8
作者：
Cho, HS;Mason, K;Leahy, DJ
通讯作者：
Leahy, DJ
影响因子：
3
作者：
Cervera, Magdalena;Esteban, Olga;Cambra, Mariano
通讯作者：
Cambra, Mariano
影响因子：
9.8
作者：
Gijsen M;King P;Perera T;Parker PJ;Harris AL;Larijani B;Kong A
通讯作者：
Kong A