Kushnir N, Streatfield SJ, Yusibov V (2012) Virus-like particles as a highly efficient vaccine
platform: diversity of targets and production systems and advances in clinical development.
Vaccine 31(1):58–83. https://doi.org/10.1016/j.vaccine.2012.10.083
Lai H, Engle M, Fuchs A, Keller T, Johnson S, Gorlatov S, Diamond MS, Chen Q (2010)
Monoclonal antibody produced in plants efficiently treats West Nile virus infection in mice.
Proc Natl Acad Sci U S A 107(6):2419–2424. https://doi.org/10.1073/pnas.0914503107
Lai H, He J, Engle M, Diamond MS, Chen Q (2012) Robust production of virus-like particles and
monoclonal antibodies with geminiviral replicon vectors in lettuce. Plant Biotechnol J
10:95–104. https://doi.org/10.1111/j.1467-7652.2011.00649.x
Lai H, He J, Hurtado J, Stahnke J, Fuchs A, Mehlhop E, Gorlatov S, Loos A, Diamond MS, Chen Q
(2014) Structural and functional characterization of an anti-West Nile virus monoclonal antibody and its single-chain variant produced in glycoengineered plants. Plant Biotechnol J
12:1098–1107. https://doi.org/10.1111/pbi.12217
Landry N, Ward BJ, Trépanier S, Montomoli E, Dargis M, Lapini G, Vézina LP (2010) Preclinical
and clinical development of plant-made virus-like particle vaccine against avian H5N1
influenza. PLoS One 5(12):e15559. https://doi.org/10.1371/journal.pone.0015559
Landry N, Pillet S, Favre D, Poulin JF, Trépanier S, Yassine-Diab B, Ward BJ (2012) Influenza
virus-like particle vaccines made in Nicotiana benthamiana elicit durable, poly-functional and
cross-reactive T cell responses to influenza HA antigens. Clin Immunol 154(2):164–177. https://
doi.org/10.1016/j.clim.2014.08.003
Lee JE, FuscoML HAJ, Oswald WB, Burton DR, Saphire EO (2008) Structure of the Ebola virus
glycoprotein bound to an antibody from a human survivor. Nature 454:177–182. https://doi.org/
10.1038/nature07082
Lee JW, Heo W, Lee J, Jin N, Yoon SM, Park KY, Kim EY, Kim WT, Kim JY (2018) The B
cell death function of obinutuzumab-HDEL produced in plant (Nicotiana benthamiana L.)
is equivalent to obinutuzumab produced in CHO cells. PLoS One 13(1):e0191075. https://doi.
org/10.1371/journal.pone.0191075
Li JF, Norville JE, Aach J, McCormack M, Zhang D, Bush J, Church GM, Sheen J (2013)
Multiplex and homologous recombination-mediated genome editing in Arabidopsis and
Nicotiana benthamiana using guide RNA and Cas9. Nat Biotechnol 31(8):688–691. https://
doi.org/10.1038/nbt.2654
Lienard D, Sourrouille C, Gomord V, Faye L (2007) Pharming and transgenic plants. Biotechnol
Annu Rev 13:115–147. https://doi.org/10.1016/S1387-2656(07)13006-4
List T, Neri D (2013) Immunocytokines: a review of molecules in clinical development for cancer
therapy. Clin Pharmacol 5:29–45. https://doi.org/10.2147/CPAA.S49231
Loh HS, Green BJ, Yusibov V (2017) Using transgenic plants and modified plant viruses for
the development of treatments for human diseases. Curr Opin Virol 26:81–89. https://doi.org/
10.1016/j.coviro.2017.07.019
Ma JK, Hiatt A, Hein M, Vine ND, Wang F, Stabila P, van Dolleweerd C, Mostov K, Lehner T
(1995) Generation and assembly of secretory antibodies in plants. Science 268(5211):716–719
Ma JK, Drake PM, Christou P (2003) The production of recombinant pharmaceutical proteins in
plants. Nat Rev Genet 4(10):794–805. https://doi.org/10.1038/nrg1177
Ma JK, Drossard J, Lewis D, Altmann F, Boyle J, Christou P, Cole T, Dale P, van Dolleweerd CJ,
Isitt V, Katinger D, Lobedan M, Mertens H, Paul MJ, Rademacher T, Sack M, Hundleby PA,
Stiegler G, Stoger E, Twyman RM, Vcelar B, Fischer R (2015) Regulatory approval and a firstin-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants.
Plant Biotechnol J 13(8):1106–1120. https://doi.org/10.1111/pbi.12416
Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R,
Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T,
Herold M, Hiddemann W (2017) Obinutuzumab for the first-line treatment of follicular
lymphoma. N Engl J 377(14):1331–1344. https://doi.org/10.1056/NEJMoa1614598
Marillonnet S, Giritch A, Gils M, Kandzia R, Klimyuk V, Gleba Y (2004) In planta engineering
of viral RNA replicons: efficient assembly by recombination of DNA modules delivered by
Agrobacterium. PNAS 101:6852–6857
102
S. Massa et al.
platform: diversity of targets and production systems and advances in clinical development.
Vaccine 31(1):58–83. https://doi.org/10.1016/j.vaccine.2012.10.083
Lai H, Engle M, Fuchs A, Keller T, Johnson S, Gorlatov S, Diamond MS, Chen Q (2010)
Monoclonal antibody produced in plants efficiently treats West Nile virus infection in mice.
Proc Natl Acad Sci U S A 107(6):2419–2424. https://doi.org/10.1073/pnas.0914503107
Lai H, He J, Engle M, Diamond MS, Chen Q (2012) Robust production of virus-like particles and
monoclonal antibodies with geminiviral replicon vectors in lettuce. Plant Biotechnol J
10:95–104. https://doi.org/10.1111/j.1467-7652.2011.00649.x
Lai H, He J, Hurtado J, Stahnke J, Fuchs A, Mehlhop E, Gorlatov S, Loos A, Diamond MS, Chen Q
(2014) Structural and functional characterization of an anti-West Nile virus monoclonal antibody and its single-chain variant produced in glycoengineered plants. Plant Biotechnol J
12:1098–1107. https://doi.org/10.1111/pbi.12217
Landry N, Ward BJ, Trépanier S, Montomoli E, Dargis M, Lapini G, Vézina LP (2010) Preclinical
and clinical development of plant-made virus-like particle vaccine against avian H5N1
influenza. PLoS One 5(12):e15559. https://doi.org/10.1371/journal.pone.0015559
Landry N, Pillet S, Favre D, Poulin JF, Trépanier S, Yassine-Diab B, Ward BJ (2012) Influenza
virus-like particle vaccines made in Nicotiana benthamiana elicit durable, poly-functional and
cross-reactive T cell responses to influenza HA antigens. Clin Immunol 154(2):164–177. https://
doi.org/10.1016/j.clim.2014.08.003
Lee JE, FuscoML HAJ, Oswald WB, Burton DR, Saphire EO (2008) Structure of the Ebola virus
glycoprotein bound to an antibody from a human survivor. Nature 454:177–182. https://doi.org/
10.1038/nature07082
Lee JW, Heo W, Lee J, Jin N, Yoon SM, Park KY, Kim EY, Kim WT, Kim JY (2018) The B
cell death function of obinutuzumab-HDEL produced in plant (Nicotiana benthamiana L.)
is equivalent to obinutuzumab produced in CHO cells. PLoS One 13(1):e0191075. https://doi.
org/10.1371/journal.pone.0191075
Li JF, Norville JE, Aach J, McCormack M, Zhang D, Bush J, Church GM, Sheen J (2013)
Multiplex and homologous recombination-mediated genome editing in Arabidopsis and
Nicotiana benthamiana using guide RNA and Cas9. Nat Biotechnol 31(8):688–691. https://
doi.org/10.1038/nbt.2654
Lienard D, Sourrouille C, Gomord V, Faye L (2007) Pharming and transgenic plants. Biotechnol
Annu Rev 13:115–147. https://doi.org/10.1016/S1387-2656(07)13006-4
List T, Neri D (2013) Immunocytokines: a review of molecules in clinical development for cancer
therapy. Clin Pharmacol 5:29–45. https://doi.org/10.2147/CPAA.S49231
Loh HS, Green BJ, Yusibov V (2017) Using transgenic plants and modified plant viruses for
the development of treatments for human diseases. Curr Opin Virol 26:81–89. https://doi.org/
10.1016/j.coviro.2017.07.019
Ma JK, Hiatt A, Hein M, Vine ND, Wang F, Stabila P, van Dolleweerd C, Mostov K, Lehner T
(1995) Generation and assembly of secretory antibodies in plants. Science 268(5211):716–719
Ma JK, Drake PM, Christou P (2003) The production of recombinant pharmaceutical proteins in
plants. Nat Rev Genet 4(10):794–805. https://doi.org/10.1038/nrg1177
Ma JK, Drossard J, Lewis D, Altmann F, Boyle J, Christou P, Cole T, Dale P, van Dolleweerd CJ,
Isitt V, Katinger D, Lobedan M, Mertens H, Paul MJ, Rademacher T, Sack M, Hundleby PA,
Stiegler G, Stoger E, Twyman RM, Vcelar B, Fischer R (2015) Regulatory approval and a firstin-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants.
Plant Biotechnol J 13(8):1106–1120. https://doi.org/10.1111/pbi.12416
Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R,
Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T,
Herold M, Hiddemann W (2017) Obinutuzumab for the first-line treatment of follicular
lymphoma. N Engl J 377(14):1331–1344. https://doi.org/10.1056/NEJMoa1614598
Marillonnet S, Giritch A, Gils M, Kandzia R, Klimyuk V, Gleba Y (2004) In planta engineering
of viral RNA replicons: efficient assembly by recombination of DNA modules delivered by
Agrobacterium. PNAS 101:6852–6857
102
S. Massa et al.