Antibodies, PEGylation

One of the remarkable properties of PEGylation is to increase the hydrodynamic radius in order to decrease renal clearance. For example, Kubetzko et al. have reported that antibody fragments (theoretically 29 kDa) showed retention volumes corresponding to a size range of 200-300 kDa by SEC upon mono-PEGylation with... 

Although the affinity was decreased fivefold upon PEGylation, PEGylated antibody fragments showed an 8.5-fold higher accumulation in tumors than unmodified antibody fragments, because of a longer serum half-life [46]. 

Chapman, P. 2002. PEGylated antibodies and antibody fragments for improved therapy a review. Advanced Drug Delivery Reviews 54(4), 531-545. 

Another perceived view about Western drugs is the adverse effects. Western medicine is sometimes viewed as a sledgehammer method rather than the more holistic approach using TM. The costs of Western medicine can be prohibitive as well, especially for patients in countries where there are no comprehensive healthcare systems. For example, treatment with pegylated interferon for hepatitis C or antibody for colon cancer can cost tens of thousands of dollars per year. Limitations of Western drugs in some cases, such as resistance to antibiotics, also highlight problems and pave the way for people to consider TM. See Exhibit 11.3 on how GlaxoSmithKline and... 

In addition to the passive targeting of tumors due to the EPR effect, active targeting of PEGylated liposomes has also been successful. A study by Huwyler and coworkers (1996), for example, showed that coupling a monoclonal antibody to the surface of PEGylated liposomes resulted in significant transfer of the liposomes across the blood-brain barrier, which is difficult to achieve otherwise. The attached... 

In addition, the polymer-coated adenovirus particles were able to shield against antibody recognition. In another approach, the PEGylation of the adenovirus capsid protein prolonged transgene expression after systemic delivery of El-deleted adenovirus, and allowed partial readministration with native virus (50). Adenovirus has been explored as vector for the treatment of cystic fibrosis (51), for Duchenne muscular dystrophy (52), to deliver tumor suppressor genes for cancer treatment... 

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