MONOCLONAL-ANTIBODIES TO HUMAN FIBRIN - INTERACTION WITH OTHER ANIMALFIBRINS

Four monoclonal antibodies have previously been raised in our laborato ry for possible use in thrombus imaging and the targeting of thromboly tic agents. These antibodies were raised to various human fibrin-relat ed immunogens and each antibody had been selected for its specificity towards fibrin and not fibrinogen. To study further these antibodies i n animal circulation models both in vivo and in vitro, their selectivi ty towards human fibrin as opposed to other animal fibrins was examine d. In this study dissociation constants for each antibody with each of six species fibrins (human, baboon, pig, dog, sheep, and rabbit) were estimated using both fibrin clots and monolayers. Some limited data w ere also obtained with Sepharose-fibrin. Of the antibodies two (denote d 12B3B10 and 12B3A11) are seen to bind almost exclusively to human fi brin with dissociation constants of about 8 x 10(-10) M using fibrin c lots and monolayers. These same two mabs bound to baboon fibrin with a dissociation constant of 2 x 10(-9) M, while neither displayed signif icant levels of binding to the fibrins from dog, pig, sheep and rabbit . The other two antibodies investigated (1H10 and 5F3) were found to b ind well to fibrins of human, baboon, pig and dog, with dissociation c onstants in the range of 1.4-4.2 x 10(-9) M. However neither 1H10 nor 5F3 displayed significant recognition of sheep and rabbit fibrins. Bot h 1H10 and 5F3 were also found by means of competitive ELISA's to reta in their selectivity to baboon, dog and pig fibrins in the presence of their respective fibrinogens.