Antibodies brain targeting

Generate therapeutic antibodies to target Ap for destruction, similar to the example of Herceptin s mechanism of action but it may be difficult to deliver large protein molecules across the blood-brain barrier of the tightly packed endothelial cells. 

Penichet ML, et al. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting initial applications in anti-HIV antisense drug delivery to the brain. J Immunol 1999 163(8) 4421—4426. 

Shin, S.U., et al. 1995. Transferrin-antibody fusion proteins are effective in brain targeting. Proc Natl Acad Sci USA 92 2820. 

Sumbria RK, Hui EK, Lu JZ (2013) Disaggregation of amyloid plaque in brain of Alzheimer s disease transgenic mice with daily subcutaneous administration of a tetravalent bi-specific antibody that targets the transferrin receptor and the Abeta amyloid peptide. Mol Pharm. doi 10.1021/mp400348n... 

Tissue targeting may also be directed at tumors through the use of monoclonal antibodies, as briefly mentioned earlier. Finally, brain targeting can also be attempted with the prodrug approach, as exemplified by estradiol by use of a redox-based chemical delivery system (174). 

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... 

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