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Special Issue Article

Production of the Human Anti-Metastatic Melonoma Interleukin-2 in Maize Vegetative Biomass for Clinical Use

Thang Xuan Nguyen, Hussien Alameldin, Patrick Thomas and Mariam Sticklen*
Department of Plant, Soil and Microbial Sciences, Michigan State University, 361 Plant Soil Sciences Building, East Lansing, MI 48824, USA
Corresponding Author : Mariam Sticklen
Department of Crop
Soil and Microbial Sciences
Michigan State University
East Lansing, MI 48824, USA
Tel: 517-230- 2929
E-mail: Stickle1@msu.edu
Received November 29, 2014; Accepted May 20, 2015; Published May 22, 2015
Citation: Nguyen TX, Alameldin H, Thomas P, Sticklen M (2015) Production of the Human Anti-Metastatic Melonoma Interleukin-2 in Maize Vegetative Biomass for Clinical Use. Adv Crop Sci Tech S1:002. doi: 10.4172/2329-8863.1000S1-002
Copyright: ©2015 Nguyen TX, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

The E.coli produced recombinant human interleukin-2 (rhIL-2) has been approved by the Food and Drug Administration for the immunotherapeutic treatment of the end-stage metastatic melanoma and renal cell cancer. However, the E.coli produced rhIL-2 is very expensive (~$11,400 USD per treatment). In the present study, we explored the feasibility of producing rhIL-2 in transgenic Zea mays (maize) vegetative biomass instead of its production in E. coli because (1) maize vegetative biomass is abundant, (2) maize can cheaply produce recombinant proteins while obtaining its energy from freely available sun via photosynthesis, has an easy scale-up via reproduction system, can be easily grown by farmers in the field with minimum level of training, and has conserved protein folding machinery including glycosylation similar to that of human. The human hIL-2 gene was codon optimized to maximize its expression in plants. A plasmid construct containing the rhIL-2 regulated by a rubisco green-specific promoter, an endoplasmic reticulum-specific signal peptide, 6-histodin tag was developed and nos terminator The construct was transferred into the maize genome via the gene gun bombardment, and fertile plants developed. Molecular analysis confirmed that the human IL-2 had integrated, transcribed and translated in up to the 4th (T3) generation maize plants. When the same gene construct was transferred into the tobacco genome and the rhIL-2 was purified and its biological activity compared with the FDA approved commercially available E coli- produced version against the marine splenic CD4+ the mice cells, the plant-produced version was as effective as the commercially available E. coli-produced version. Research is needed to test the rhIL-2 producing maize in the field, and to perform preclinical and clinical trial for its potential commercial release.

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