(β-glucan), both 2G8 chimeric IgG and scFv-Fc produced in plants retained the
efficacy of the original mAb, being able to inhibit directly the growth of Candida
albicans and to induce protection in animal models mimicking a systemic or vaginal
C. albicans infection. In addition, both Abs promoted the killing of fungal cells by
human polymorphonuclear neutrophils in ex vivo assays. In a further development, a
recombinant IgA version was also expressed and correctly assembled in dimeric
form in plants (Capodicasa et al. 2017). These recombinant Abs may be exploited
to tackle a broad range of human fungal infections, in alternative or in addition to
classical chemotherapy (Table 6).
5 Plant-Made Proteins for Other Pharmacological Uses
Currently, only two products derived from this technology have been brought on the
market. The first, Elelyso, is an enzyme replacement therapy (ERT) for humans,
while the second, Interberry-alpha, has been developed for veterinary use (canine
gingivitis).
In 2012, the US FDA approved ELELYSO™ (human recombinant taliglucerase
alfa or glucocerebrosidase, GC), an enzyme produced in genetically engineered
carrot cells for treating type 1 Gaucher’s disease (GD) by Protalix BioTherapeutics
(an Israeli enterprise established in 1993) and its partner, Pfizer (Fox 2012). GD is
a lysosomal storage disorder caused by a hereditary deficiency of the enzyme
glucocerebrosidase, which is involved in glycolipid metabolism. GD creates a
disabling condition curable only with permanent ERT.
As a result of advances in stable plant transformation technology and upstream
and downstream manufacturing process, GD can be currently treated by enzyme
replacement therapy using this recombinant GC that is administered intravenously
every 2 weeks (Shaaltiel et al. 2007) and represents an alternative, cheaper choice
with respect to the CHO-based manufacturing (i.e. the recombinant human GC
Cerezyme™ -Genzyme- and (VpriV
® ) -Shire Pharmaceuticals-). Moreover, since
expression of taliglucerase alfa is targeted to the storage vacuoles of the cell using a
plant-specific sorting signal, this determines the presence of mannose sugars. In fact,
GC utilized for ERT must display mannose moieties for entry into the macrophage.
The expression process in the plant cell results in mannose decoration without
glycan enzymatic remodelling, which is, instead, a downstream process necessary
for drug of mammalian cell origin elevating the cost of goods for this specific
product. Protalix brilliantly took advantage of the plant secretory pathway to
obtain homogeneous paucimannosidic glycans in a cost-effective glycoengineering
intervention within the cells. A fortunate circumstance to speed up ELELYSO
approval was the US FDA warning about the potential for foreign-particle contamination in some Genzyme products including Cerezyme™ (Drake et al. 2017). This
event has been fundamental to raise awareness of the scarcity of approved safer
alternatives to mammalian cell manufacturing. Moreover, it sets a positive example
to be followed that could renew investors’ interest in molecular farming companies,
similar to what has occurred right after commercial approval for ELELYSO that
90
S. Massa et al.
efficacy of the original mAb, being able to inhibit directly the growth of Candida
albicans and to induce protection in animal models mimicking a systemic or vaginal
C. albicans infection. In addition, both Abs promoted the killing of fungal cells by
human polymorphonuclear neutrophils in ex vivo assays. In a further development, a
recombinant IgA version was also expressed and correctly assembled in dimeric
form in plants (Capodicasa et al. 2017). These recombinant Abs may be exploited
to tackle a broad range of human fungal infections, in alternative or in addition to
classical chemotherapy (Table 6).
5 Plant-Made Proteins for Other Pharmacological Uses
Currently, only two products derived from this technology have been brought on the
market. The first, Elelyso, is an enzyme replacement therapy (ERT) for humans,
while the second, Interberry-alpha, has been developed for veterinary use (canine
gingivitis).
In 2012, the US FDA approved ELELYSO™ (human recombinant taliglucerase
alfa or glucocerebrosidase, GC), an enzyme produced in genetically engineered
carrot cells for treating type 1 Gaucher’s disease (GD) by Protalix BioTherapeutics
(an Israeli enterprise established in 1993) and its partner, Pfizer (Fox 2012). GD is
a lysosomal storage disorder caused by a hereditary deficiency of the enzyme
glucocerebrosidase, which is involved in glycolipid metabolism. GD creates a
disabling condition curable only with permanent ERT.
As a result of advances in stable plant transformation technology and upstream
and downstream manufacturing process, GD can be currently treated by enzyme
replacement therapy using this recombinant GC that is administered intravenously
every 2 weeks (Shaaltiel et al. 2007) and represents an alternative, cheaper choice
with respect to the CHO-based manufacturing (i.e. the recombinant human GC
Cerezyme™ -Genzyme- and (VpriV
® ) -Shire Pharmaceuticals-). Moreover, since
expression of taliglucerase alfa is targeted to the storage vacuoles of the cell using a
plant-specific sorting signal, this determines the presence of mannose sugars. In fact,
GC utilized for ERT must display mannose moieties for entry into the macrophage.
The expression process in the plant cell results in mannose decoration without
glycan enzymatic remodelling, which is, instead, a downstream process necessary
for drug of mammalian cell origin elevating the cost of goods for this specific
product. Protalix brilliantly took advantage of the plant secretory pathway to
obtain homogeneous paucimannosidic glycans in a cost-effective glycoengineering
intervention within the cells. A fortunate circumstance to speed up ELELYSO
approval was the US FDA warning about the potential for foreign-particle contamination in some Genzyme products including Cerezyme™ (Drake et al. 2017). This
event has been fundamental to raise awareness of the scarcity of approved safer
alternatives to mammalian cell manufacturing. Moreover, it sets a positive example
to be followed that could renew investors’ interest in molecular farming companies,
similar to what has occurred right after commercial approval for ELELYSO that
90
S. Massa et al.