which currently have limited access to these biologics, due to the current costs of
manufacturing in mammalian cell culture. This scenario would unlock the full
potential of plants as a novel production platform.
mAbs directed to several tumour-associated antigens (Table 6) and involved in
different mechanisms of interference/diagnosis of the relevant cancer type have been
expressed in both plant leaves and seeds (Pujol et al. 2007). The genes for heavy
and light chain of the base format of the immunoglobulin have been engineered for
transient or stable expression through different techniques of transgenesis involving
both nuclear and chloroplast genome (Ko et al. 2005; Komarova et al. 2010; Daniell
2003).
As mentioned elsewhere in this chapter, every expression technique (either stable
or transient) presents advantages and drawbacks. Therefore, a careful evaluation
of the system has to be adopted on a case-by-case basis. Nevertheless, while
cumbersome procedures are required for the establishment of stable genome transgenic lines and literature highlights expression yields usually non-competitive
(De Muynck et al. 2010), transient expression systems allow high yields of recombinant protein in few days. The transient approach has been prevalent in recent years
in an attempt to make the plant system highly productive for the synthesis of biologic
medicines. As an example, by this approach it is currently possible to produce ten
million doses of influenza vaccine in the remarkable time of 6 weeks (Pillet et al.
2016).
In a pioneering work of agro-infiltration, a clinically relevant recombinant antibody (diabody) against the carcinoembryonic antigen (CEA) in tumour imaging was
expressed in tobacco plants (Vaquero et al. 2002) validating the feasibility of the
approach. In subsequent study, 500 mg/kg yields of a full-size tumour-specific
human mAb A5 were achieved using the “MagnICON” system (magnifection)
developed by Icon Genetics (Giritch et al. 2006; Marillonnet et al. 2004).
Since the discovery of competitive manufacturing yields, anticancer therapeutic
antibodies produced as plant biosimilars occupy an area of active interest due to the
potential to guarantee access to more affordable treatments also in view of patents’
expiry dates for quite a number of antibodies by 2020. The following examples
witness a fervent activity in this sense.
TheraCIM, a recombinant humanized antibody against the epidermal growth
factor receptor (EGF-R) that had orphan drug status for glioma, starting from 2014
in the United States and EU, was one of the first antibodies of commercial value to be
transiently expressed in plants. Engineered in an aglycosylated format in tobacco,
this antibody, produced from agro-infiltrated leaves, maintained unchanged the
recognition of the EGF-R on the surface of human tumour cultured cells (Rodriguez
et al. 2005).
Trastuzumab, a humanized monoclonal approved by the US Food and Drug
Administration for the treatment of metastatic breast cancer, recognizing the
human epidermal growth factor receptor 2 (HER2/neu), has been transiently
expressed in N. benthamiana plants (Komarova et al. 2011; Grohs et al. 2010).
In these independent reports, this plant-made mAb, expressed using either the
Engineering Plants for the Future: Farming with Value-Added Harvest
85
manufacturing in mammalian cell culture. This scenario would unlock the full
potential of plants as a novel production platform.
mAbs directed to several tumour-associated antigens (Table 6) and involved in
different mechanisms of interference/diagnosis of the relevant cancer type have been
expressed in both plant leaves and seeds (Pujol et al. 2007). The genes for heavy
and light chain of the base format of the immunoglobulin have been engineered for
transient or stable expression through different techniques of transgenesis involving
both nuclear and chloroplast genome (Ko et al. 2005; Komarova et al. 2010; Daniell
2003).
As mentioned elsewhere in this chapter, every expression technique (either stable
or transient) presents advantages and drawbacks. Therefore, a careful evaluation
of the system has to be adopted on a case-by-case basis. Nevertheless, while
cumbersome procedures are required for the establishment of stable genome transgenic lines and literature highlights expression yields usually non-competitive
(De Muynck et al. 2010), transient expression systems allow high yields of recombinant protein in few days. The transient approach has been prevalent in recent years
in an attempt to make the plant system highly productive for the synthesis of biologic
medicines. As an example, by this approach it is currently possible to produce ten
million doses of influenza vaccine in the remarkable time of 6 weeks (Pillet et al.
2016).
In a pioneering work of agro-infiltration, a clinically relevant recombinant antibody (diabody) against the carcinoembryonic antigen (CEA) in tumour imaging was
expressed in tobacco plants (Vaquero et al. 2002) validating the feasibility of the
approach. In subsequent study, 500 mg/kg yields of a full-size tumour-specific
human mAb A5 were achieved using the “MagnICON” system (magnifection)
developed by Icon Genetics (Giritch et al. 2006; Marillonnet et al. 2004).
Since the discovery of competitive manufacturing yields, anticancer therapeutic
antibodies produced as plant biosimilars occupy an area of active interest due to the
potential to guarantee access to more affordable treatments also in view of patents’
expiry dates for quite a number of antibodies by 2020. The following examples
witness a fervent activity in this sense.
TheraCIM, a recombinant humanized antibody against the epidermal growth
factor receptor (EGF-R) that had orphan drug status for glioma, starting from 2014
in the United States and EU, was one of the first antibodies of commercial value to be
transiently expressed in plants. Engineered in an aglycosylated format in tobacco,
this antibody, produced from agro-infiltrated leaves, maintained unchanged the
recognition of the EGF-R on the surface of human tumour cultured cells (Rodriguez
et al. 2005).
Trastuzumab, a humanized monoclonal approved by the US Food and Drug
Administration for the treatment of metastatic breast cancer, recognizing the
human epidermal growth factor receptor 2 (HER2/neu), has been transiently
expressed in N. benthamiana plants (Komarova et al. 2011; Grohs et al. 2010).
In these independent reports, this plant-made mAb, expressed using either the
Engineering Plants for the Future: Farming with Value-Added Harvest
85