CONTROLLED DELIVERY OF ANTIBODIES AGAINST LEUKOCYTE ADHESION MOLECULES FROM POLYMER MATRICES

The interaction between infected leukocytes and mucosal epithelia is l ikely to play a critical role in the sexual transmission of certain di seases. It may be possible to prevent the transmission of intracellula r pathogens by inhibiting leukocyte-epithelial interactions. Monoclona l antibodies (MAbs) against leukocyte adhesion receptors can provide s pecific and potent inhibition of leukocyte-epithelial interactions, bu t systemic delivery of such MAbs is not desirable; therefore, a new me thod for local delivery of anti-adhesion MAbs to an exposed mucosal su rface was developed using polymeric controlled-release devices. To eva luate the prophylactic potential of MAbs, leukocyte adhesion to the ap ical surface of a monolayer of T84 cells was examined in the presence of MAbs against human leukocyte surface proteins. MAbs against the MAC -I adhesion receptor inhibited neutrophil attachment to T84 cells by a s much as 97%. MAbs against murine leukocyte receptors were produced f rom several hybridomas and incorporated into poly(ethylene-co-vinyl ac etate) (EVAc) devices. During incubation in buffered saline, small pol ymer discs continuously released active MAbs for 10 days. After insert ion into the vaginal canals of mice, these polymer disks produced high levels of anti-MAC-1 MAb for several days. Polymeric controlled-relea se devices provide a new technique for using MAbs against adhesion rec eptors as a means of long-term, localized sexually transmitted disease (STD) prophylaxis.