BISPECIFIC ANTIBODY FOR DIRECTED DELIVERY OF PALYTOXIN

CONSIDERABLE INTEREST HAS BEEN FOCUSSED ON THE PRODUCTION AND CHARACTERIZATION OF THERAPEUTIC IMMUNOCONJUGATES. SUCH HYBRID MOLECULES USUALLY CONSIST OF A MONOCLONAL ANTIBODY WITH COVALENTLY ATTACHED TOXIN, DRUG, OR RADIOISOTOPE. SOME OF THESE AGENTS HAVE BEEN SHOWN TO BE CLINICALLY USEFUL FOR IMMUNOSUPPRESSION OR CANCER TREATMENT. HOWEVER, THESE COVALENTLY LINKED IMMUNOCONJUGATES ALSO SUFFER FROM DRAWBACKS. COVALENT MODIFICATION OF TOXINS AND DRUGS OFTEN REDUCES THEIR POTENCY. IN ADDITION, MANY OF THE PROTEIN TOXINS USED FOR THIS PURPOSE ARE IMMUNOGENIC. ANOTHER APPROACH FOR THE SELECTIVE DELIVERY OF CYTOTOXIC AGENTS IS TO USE BISPECIFIC ANTIBODIES. RECENTLY REPORTED METHODS ALLOW SELECTIVE LINKAGE OF ANTIBODY FRAGMENTS, SUCH THAT F(AB' GAMMA)2 WITH DUAL ANTIGEN SPECIFICITY ARE PRODUCED IN HIGH YIELD. PALYTOXIN IS THE MOST POTENT NON-PROTEINACEOUS TOXIN DESCRIBED AND IS OF COMPARATIVELY LOW MOLECULAR WEIGHT (2678.5G/MOL). THESE ATTRIBUTES MAKE PALYTOXIN AN ATTRACTIVE CANDIDATE FOR SITE-DIRECTED CELL ABLATIVE THERAPIES. THIS ORGANIZATION HAS PREPARED MONOCLONAL ANTIBODIES TO PALYTOXIN. WE WILL CONSTRUCT BISPECIFIC F(AB' GAMMA)2 DERIVED FROM THESE MONOCLONAL ANTIBODIES AND FROM MONOCLONAL ANTIBODIES REACTIVE WITH CD4 HUMAN T-CELL ANTIGEN. THESE BISPECIFIC ANTIBODIES WILL BE TESTED IN VITRO FOR DIRECTED SELECTIVE KILLING OF CELLS EXPRESSING CD4 ANTIGEN.