Conjugation of plasminogen activators and fibrin-specific antibodies to improve thrombolytic therapeutic agents.
Here we have reviewed chemical and recombinant approaches to the construction of hybrid molecules that combine a "targeting" antibody and an "effector" enzyme activity. There are advantages and disadvantages to both chemical and recombinant methods, and one goal of this review has been to elucidate these so that the appropriate method can be used by those interested in using hybrid molecules to study questions of basic or therapeutic importance. The system studied in greatest detail has as its goal the targeting of a plasminogen activator to an occlusive intravascular thrombus. We have, therefore, used this system as an example of currently available approaches. Now that these methodologies have been studied and put into use, it is anticipated that this principle will be generalized both to other therapeutic applications, as well as to the design and construction of molecules that will allow more basic questions to be addressed.
Hayzer
D J
DJ
Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322.
Lubin
I M
IM
Runge
M S
MS
D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005337:Fibrin / Q000276:immunology*; D006801:Humans; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000737:chemistry; D015912:Thrombolytic Therapy
D000906:Antibodies; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D011994:Recombinant Proteins; D005337:Fibrin; D010960:Plasminogen Activators