Search PubMed⌕ Search

Biomedical subjects

M S Runge

Publications and source records attributed to M S Runge.

131 records · Page 8Linked to original sources
PubMedDate not supplied

Antibody-directed fibrinolysis: a bispecific (Fab')2 that binds to fibrin and tissue plasminogen activator.

A bispecific (Fab')2 molecule was constructed by linking the monovalent Fab' from an anti-fibrin monoclonal antibody to the Fab' from an anti tissue plasminogen activator (tPA, single chain) monoclonal antibody by means of inter-heavy-chain disulfide bonds. An immunochemical complex composed of the bispecific (Fab')2 molecule bound to tPA [tPA-bispecific (Fab')2 complex] was then generated and purified. Its molecular weight was 170 kDa [less than half the molecular weight of a previously described tPA-bispecific antibody complex containing the entire anti-fibrin and anti-tPA immunoglobulin molecules; Runge, M. S., et al. (1987) Trans. Assoc. Am. Phys. 100, 250-255]. The tPA-bispecific (Fab')2 complex was 8.6-fold more efficient in fibrinolysis than tPA alone and 94-fold more potent than urokinase. This enhancement in the fibrinolytic potency of tPA compares favorably with that observed for the bispecific whole-antibody complex. These results suggest that this smaller, less immunogenic molecule is capable of binding both fibrin and tPA with high affinity and of enhancing the thrombolytic efficiency of exogenous and, perhaps, endogenous tPA.

Antibodies, Monoclonal↗
PubMedDate not supplied

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.

Animals↗