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免疫病理疾病及治疗学论文学
SJR: 0.164 SNIP: 0.041 CiteScore™: 0.18

ISSN 打印: 2151-8017
ISSN 在线: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

免疫病理疾病及治疗学论文学

DOI: 10.1615/ForumImmunDisTher.2014008241
pages 241-254

Algal-Produced Immunotoxins

Miller Tran
Verdant Therapeutics, San Francisco, California
James S. Hyun
Division of Molecular Biology, The California Center for Algae Biotechnology, University of California, San Diego, California
Michael P. Mayfield
Verdant Therapeutics, San Francisco, California
Jonathan L. Torres
Division of Molecular Biology, The California Center for Algae Biotechnology, University of California, San Diego, California
Amy T. Hoang
Division of Molecular Biology, The California Center for Algae Biotechnology, University of California, San Diego, California
Stephen P. Mayfield
Division of Molecular Biology, The California Center for Algae Biotechnology, University of California, San Diego, California

ABSTRACT

Antibody drug conjugates (ADCs) and immunotoxins are second-generation anticancer therapeutics that directly target cancerous cells and deliver toxic molecules that inhibit the cancer's proliferation. They are composed of an antibody domain that binds the target cell, linked to a toxic molecule that inhibits cell proliferation. Utilization of these potent and effective therapies is limited by the high cost and complexity of manufacturing these chimeric molecules. ADCs are currently made by chemically linking an antibody produced by a mammalian cell culture to a toxic drug molecule. Unlike ADCs, immunotoxins utilize protein toxins derived from bacteria or plants, and are often genetically linked to the antibody domain. Protein toxins typically target eukaryotic translations. Because these toxins target eukaryotic translation, they cannot be produced in eukaryotic expression. Production of these chimeric molecules in bacteria is also limited due to the lack of sophisticated protein-folding machinery, which is required to fold complex immunotoxin proteins. To overcome the challenges associated with the production of immunotoxins, chloroplasts of the eukaryotic green alga Chlamydomonas reinhardtii were recently developed as an expression host. Chloroplasts contain complex protein-folding machinery, including chaperones and protein disulfide isomerases, but have a translational apparatus (70S ribosomes and elongation factors) that resembles that of a bacterium, leaving them unharmed by toxins that target the eukaryotic translational apparatus. In addition, chloroplasts are capable of producing multivalent immunotoxins, which increases the capability of these molecules to inhibit the proliferation of cancer cells. Development of this new technology will allow the production of more complex and effective immunotoxins, while potentially reducing the complexity of production of these valuable cancer therapies.


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