BEH. 462/3.962J Molecular Principles of Biomaterials Spring 2003 Targeting Approaches- Targeted delivery receptor-Iigand-based targetin o/iigand pairs neral cell surface recept guide drug to target based on unique or over-expressed receptor on target cell type over-expressed in 95% of of non-mucinous ovan nian carcinomas high affinity (-1 nM Ko- typical half-life at 37C?) cons need to be humanized to avoid rapid opsonization on only variable region of mouse antibody need be retained for antigen recognition need to consider possible Fc receptor binding use of FAb fragments as an alternative source of ab 3d animation http://digilander.liberoit/danielefocosi/immunity.html#but,%20on%20the%20contrary%20of%20t CR,%20other%20BCR%20isotypes Key featuree of the protein atructure of (human lg G,)immunoglobulin molecules Fc receptor FAb/FAbO macrophage Lecture 17-Drug targeting 2 of 7BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Targeting Approaches4 Targeted delivery ƒ receptor-ligand-based targeting o general cell surface receptor-ligand pairs ƒ guide drug to target based on unique or over-expressed receptor on target cell type ƒ folate receptor • over-expressed in 95% of non-mucinous ovarian carcinomas5 o antibody targeting ƒ pros • high affinity (~1 nM KD- typical half-life at 37°C?) • high specificity ƒ cons • need to be ‘humanized’ to avoid rapid opsonization o only variable region of mouse antibody need be retained for antigen recognition • need to consider possible Fc receptor binding o Fc = ‘fragment crystallizable’ • use of FAb fragments as an alternative ƒ source of Ab 3D animation: http://digilander.libero.it/danielefocosi/immunity.html#But,%20on%20the%20contrary%20of%20T cR,%20other%20BcR%20isotypes QuickTime™ and a GIF decompressor are needed to see this picture. Fc Fc receptor macrophage FAb/FAbÕ -SH Lecture 17 – Drug targeting 2 of 7