CROSS-LINKED BISPECIFIC MONOCLONAL-ANTIBODY HETEROPOLYMERS FACILITATETHE CLEARANCE OF HUMAN-IGM FROM THE CIRCULATION OF SQUIRREL-MONKEYS

We have previously demonstrated that cross-linked bispecific monoclona l antibodies (mAb) heteropolymers (HP), specific for primate erythrocy te (E) complement receptor type 1 (CR1) and target antigen (Ag), facil itate the binding of these target Ag to human and non-human primate E. Once bound in vitro to rhesus monkey E, upon re-infusion these HP/Ag complexes are recognized in vivo by cells of the reticuloendothelial s ystem (RES) and removed from the circulation without loss of the E. We now show, in squirrel monkeys, that an HP specific for E CR1 and huma n IgM (anti-CR1 x anti-IgM) can be used to facilitate in vivo E bindin g and clearance from the circulation of a previously injected and circ ulating model protein pathogen, human IgM. Approximately 70-80% of I-1 25-labeled human IgM is cleared from the circulation of each of five s quirrel monkeys via the HP system. We observe, in experiments analogou s to previous studies on immune complex (IC) clearance, that subsequen t to HP/Ag clearance there is a decrease in the number of CR1 epitopes per E which is manifested when we use both monoclonal and polyclonal anti-CR1 probes. Our results indicate that the primary organs responsi ble for uptake of the complexes are the liver and spleen. This work st rongly suggests that the HP/Ag complexes, bound to E, function as IC p rototypes and are recognized and processed as such in vivo. Thus, the HP-E system may eventually serve as a viable immunotherapy for the cle arance of blood-borne pathogens from the circulation.