Antibodies from transgenic animals

Longberg, N. 2005. Human antibodies from transgenic animals. Nature Biotechnology 23(9), 1117-1125. 

Bovine colostrum as well as milk whey contain essentially bacteria and pyrogenic substances and may contain viruses. Humanized or specifically reconstructed antibodies from transgenic animals can contain traces of endogenous antibodies from the host animal that are very difficult to separate from the newly expressed molecules. 

Lonberg, N. (2005). Human antibodies from transgenic animals. Nat. Biotechnol. 23,1117-1125. Lonnerdal, B. (1996). Recombinant human milk proteins- an opportunity and a challenge. 

Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use Points to Consider on Plasmid DNA Vaccines for Preventive Infectious Disease Indications Points to Consider in the Manufacture and Testing of Therapeutic Products for Human Use Derived from Transgenic Animals... 

Due to discrimination from species to species, protein A resins can be used to separate monoclonal antibodies from transgenic milk. Autologous antibodies are not adsorbed if the animal is well chosen. For instance, monoclonal humanized IgG expressed in goat milk can be separated. 

Easiest are sections from transgenic animals with GFP tagged to the protein, which shows colocalization (Fig. 8.2b). A second approach is to use a second 1° antibody made to the same antigen, which should show colocalization. In many cases, antibodies to different parts of the amino acid sequence on a single protein antigen use different epitopes on the same antigen and should show 100% colocalization (Fig. 8.2c). This is indirect evidence because it does not show the identical protein bound by the 1° antibody and other antibodies it only shows the same location is labeled but not necessarily the same protein. 

Overexpression of the EGF receptor (or any of its ligands), can also induce cancer in both cell lines and transgenic animal models. Monoclonal antibodies capable of blocking receptor activity can promote tumour regression in mice suffering from various carcinomas. A direct correlation also exists between elevated EGF receptor numbers and a shorter patient survival span in the case of several forms of breast, oesophageal, bladder and squamous cell carcinomas. 

The main focus on modem biopharmaceuticals should be directed towards novel products which will be either monoclonal antibodies, recombinant proteins, cell and gene therapeutics, or viral products. Apart from product classes, new approaches to manufacture are also advancing, with transgenic animals and plants complementing existing cell culture-based expression (see Part IV, Chapters 5-11). (For a recent review, see Ref [8].)... 

PG (58). In subsequent studies (59), we isolated lung myofibroblasts from bleomycin-exposed rats and determined that these cells secreted increased amounts of TGF-pi and PG, as compared to fibroblasts from control animals. PG secretion was further enhanced by exogenous TGF-p and inhibited by anti-TGF-p antibodies and IFN-y. The role of PG is compounded by the ability of decorin to bind TGF-p, reducing its bioavailability (60). A number of studies conducted in transgenic mice have now shown that gene transfer, or transgene overexpression of decorin, can modulate bleomycin-induced lung fibrosis (61-63). 

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