1. Lecture 38 Plantibodies

2. ANTIBODIES PRODUCED FROM PLANTS
Functional antibodies can be produced from plants
Targeted to intercellular space, chloroplast, seeds and tubers
Benefit for topical immunotherapy
Can be produced from plants in large quantities
Contd...

3. Plantibodies provides increased stability
e.g: Secretory Ig A
Plants can assemble complex secretory antibodies
e.g: Construction of tobacco plants expressing 4 transgenes
Quadruple transgenics efficiently assembled secretory immunoglobulins
(Smith & Glick, 2000)

4. Anti-rabies virus mAb After exposure treated with Ab
Used to be made in horses
First mAb made in transgenic plants
4 genes – 2 H, 2 L
Transgenic plant for each one and crossing plants
Later used single binary vector with two promoters

5. Full-size monoclonal antibodies recently produced in transgenic plants

6. Abs expressed in transgenic plants
Constant domains
Variable Light chain
Variable Heavy chain
Recombinant hinge region

7. Functional Abs Need to be properly folded and assembled
Need disulfide bond formation and glycosylation
Down stream processing:
Purification of Ab mostly with Protein A or G
Glycosylation is different in plants
β 1,2 Xylose and α 1,3 fucose
Retain in ER, only mannose is attached
Shorter half-life of Ab

8. Glycosylation of Ab Full-size Ab Large single-chain Ab
Camelid heavy-chain Ab
Minibodies and Fab fragments don’t get glycosylated

9. Glycosylation in Golgi

10. Antibodies: a compelling success story
high specificity: in vitro and in vivo diagnostics
low toxicity: therapeutic applications
high drug approval rates (24 approved mAbs)
major products in biotechnology (~240 in clinical trials)
inherently stable human proteins
injectable, topical and oral applications
applicable for chronic conditions
potential long-lasting benefits

11. Production Costs for Antibodies
cost in $ /
gram
hybridomas
1000
transgenic animals
100
transgenic plants 10
Source: Daniell et al. (2001) TIPS 6,
E. coli & yeast
Tr. animals and animal cells
Transgenic plants

12. Comparison of Mammalian and Plant-produced Antibodies
peptide sequence: identical
correct cleavage of Ig-derived signal peptides
kinetics & affinity: identical
stability in seeds > 30 months
antibody types: plant system more versatile (sIgA)
post-translational processing: different
core glycan identical, terminal sugar different plus xylose & fucose
antigenicity & clearance: apparently identical (shorter half-life)