Caliber Biotherapeutics LLC declares itself ready to produce commercial quantities
of ZMapp mAbs quickly and cost-effectively. Overall efforts will potentially boost
production amounts and worldwide supply of these important drugs.
The paramyxovirus respiratory syncytial virus (RSV) can cause devastating lower
respiratory tract infections in preterm infants and small children or elderly patients
when other serious health problems are present. Passive immunization is an effective
immunoprophylaxis against RSV, and treatment with a humanized IgG1 mAb,
palivizumab (brand name Synagis, manufactured by MedImmune), is the current
standard of care. In a recent report, plant-made different isotypes and N-glycoform
variants were compared with commercially available palivizumab with respect to
both in vitro receptor and C1q binding and in vivo efficacy. Whereas the antigen
binding and neutralization activity of each variant were indistinguishable from those
of palivizumab, their Fcγ receptor binding profiles demonstrated significant differences. Overall results indicate that interaction with FcγR, hence antibody-dependent
cell-mediated cytotoxicity and not virus neutralization, plays the major role in
palivizumab’s efficacy. Therefore isotype and glycan profile engineering utilizing
glycoengineered plant hosts have been put into play, paving the way for enhancing
antibody-dependent cellular cytotoxicity and the efficacy of these anti-RSV mAbs
(with yields of ~200 mg per kilogram of plant biomass) (Hiatt et al. 2014).
Anthrax is a zoonotic disease caused by the gram-positive, spore-forming bacterium Bacillus anthracis. Although the incidence of the disease has continually
decreased since the late nineteenth century, anthrax is considered one of major
concerns in the era of bioterrorism in that inhalation of aerosolized spores has very
high mortality rates. B. anthracis possesses a main virulence factor, the 83-kDa form
of protective antigen (PA), composed of two exotoxins, also known as lethal toxin
and oedema toxin, which cause cell death following introduction into the cytoplasm
(Young and Collier 2007). PA elicits specific neutralizing antibodies and is the major
target for the development of both anthrax vaccines and mAbs. A human mAb
against the B. anthracis PA has been overexpressed in plants to be used in both
prophylactic and therapeutic treatments of individuals exposed or infected with
anthrax. A humanized glycosylated (e.g. “decorated” with plant-specific glycans)
and a glycan-deprived version of this mAb have been devised. Both formats were
able to bind PA, neutralizing anthrax lethal toxin, and to protect mice against a lethal
spore challenge. Surprisingly, the glycan-deprived mAb demonstrated improved
half-life providing full protection in non-human primates against anthrax spore
inhalation (Mett et al. 2011).
Infections caused by opportunistic fungal pathogens pose serious issues for both
prevention and treatment especially in immune-compromised or hospitalized individuals. In the perspective of being used as a wide-spectrum antifungal therapeutics,
a chimeric complete IgG and IgG-like format (scFv-Fc) have been produced
in agro-infiltrated N. benthamiana plants (Capodicasa et al. 2011). These engineered Abs were derived from a murine mAb (2G8) that inhibits fungi growth
conferring significant protection against different opportunistic pathogens such as
Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans in animal
models (Torosantucci et al. 2009). By binding to a fungal cell wall polysaccharide
Engineering Plants for the Future: Farming with Value-Added Harvest
89
of ZMapp mAbs quickly and cost-effectively. Overall efforts will potentially boost
production amounts and worldwide supply of these important drugs.
The paramyxovirus respiratory syncytial virus (RSV) can cause devastating lower
respiratory tract infections in preterm infants and small children or elderly patients
when other serious health problems are present. Passive immunization is an effective
immunoprophylaxis against RSV, and treatment with a humanized IgG1 mAb,
palivizumab (brand name Synagis, manufactured by MedImmune), is the current
standard of care. In a recent report, plant-made different isotypes and N-glycoform
variants were compared with commercially available palivizumab with respect to
both in vitro receptor and C1q binding and in vivo efficacy. Whereas the antigen
binding and neutralization activity of each variant were indistinguishable from those
of palivizumab, their Fcγ receptor binding profiles demonstrated significant differences. Overall results indicate that interaction with FcγR, hence antibody-dependent
cell-mediated cytotoxicity and not virus neutralization, plays the major role in
palivizumab’s efficacy. Therefore isotype and glycan profile engineering utilizing
glycoengineered plant hosts have been put into play, paving the way for enhancing
antibody-dependent cellular cytotoxicity and the efficacy of these anti-RSV mAbs
(with yields of ~200 mg per kilogram of plant biomass) (Hiatt et al. 2014).
Anthrax is a zoonotic disease caused by the gram-positive, spore-forming bacterium Bacillus anthracis. Although the incidence of the disease has continually
decreased since the late nineteenth century, anthrax is considered one of major
concerns in the era of bioterrorism in that inhalation of aerosolized spores has very
high mortality rates. B. anthracis possesses a main virulence factor, the 83-kDa form
of protective antigen (PA), composed of two exotoxins, also known as lethal toxin
and oedema toxin, which cause cell death following introduction into the cytoplasm
(Young and Collier 2007). PA elicits specific neutralizing antibodies and is the major
target for the development of both anthrax vaccines and mAbs. A human mAb
against the B. anthracis PA has been overexpressed in plants to be used in both
prophylactic and therapeutic treatments of individuals exposed or infected with
anthrax. A humanized glycosylated (e.g. “decorated” with plant-specific glycans)
and a glycan-deprived version of this mAb have been devised. Both formats were
able to bind PA, neutralizing anthrax lethal toxin, and to protect mice against a lethal
spore challenge. Surprisingly, the glycan-deprived mAb demonstrated improved
half-life providing full protection in non-human primates against anthrax spore
inhalation (Mett et al. 2011).
Infections caused by opportunistic fungal pathogens pose serious issues for both
prevention and treatment especially in immune-compromised or hospitalized individuals. In the perspective of being used as a wide-spectrum antifungal therapeutics,
a chimeric complete IgG and IgG-like format (scFv-Fc) have been produced
in agro-infiltrated N. benthamiana plants (Capodicasa et al. 2011). These engineered Abs were derived from a murine mAb (2G8) that inhibits fungi growth
conferring significant protection against different opportunistic pathogens such as
Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans in animal
models (Torosantucci et al. 2009). By binding to a fungal cell wall polysaccharide
Engineering Plants for the Future: Farming with Value-Added Harvest
89