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Engineered Nicotiana benthamiana to produce glycosylated IgMs

Engineered N. benthamiana could generate glycosylated IgMs to treat human diseases. In engineered N. benthamiana plants lacking plant-specific glycosylation, transfection with vectors encoding IgM components resulted in the production of a therapeutic IgM, PAT-SM6, in high picomolar yields per gram of plant material. The glycosylation pattern of the plant-generated PAT-SM6 was comparable to that of PAT-SM6 produced in a human cell line. In a human lung cancer cell line, the plant- and human cell line-generated forms of PAT-SM6 showed comparable inhibitory action against their target, heat shock 70 kDa protein 5 (glucose-regulated protein, 78 kDa; HSPA5; GRP78). Next steps include using the engineered plants to generate IgMs against antibiotic-refractory bacterial infections.
Patrys Ltd. has PAT-SM6, a human mAb that binds HSPA5 and imports low-density lipoprotein into cancer cells, in Phase I/II testing to treat multiple myeloma (MM) and Phase I trials to treat melanoma.
Patrys, AstraZeneca plc and Debiopharm Group have PAT-SC1, a human IgM mAb that binds to gastric cancer cells expressing CD55SC-1, in Phase I/II testing to treat gastric cancer and in preclinical development for solid tumors.

SciBX 7(17); doi:10.1038/scibx.2014.503
Published online May 1, 2014

Patented; licensing status undisclosed

Loos, A. et al. Proc. Natl. Acad. Sci. USA; published online March 31, 2014;
Contact: Herta Steinkellner, University of Natural Resources and Applied Life Sciences, Vienna, Austria