Cloning and expression of a novel murine anti-human Fas antibody

Agonistic anti-human Fas antibodies that can induce apoptosis are thought t o have therapeutic effects for various diseases resulting from an abnormali ty of the Fas/FasL system. However, some anti-Fas antibodies show toxicity, and it is difficult to investigate their therapeutic and toxicological eff ect using animals because of their species specificity. We previously obtai ned a murine anti-human Fas mAb, HFE7A. HFE7A reacted,vith both human and m urine Fas, and mitigated lymphadenopathy without any sign of hepatotoxicity in MRLgld/gld mice. It is suggested that humanized HFE7A would be a therap eutic treatment for various diseases resulting from an abnormality of the F as/FasL system. Here we isolated the cDNAs that code for the heavy and ligh t chains of HFE7A and identified the corresponding nucleotide sequences. Th e recombinant HFE7A was indistinguishable in binding and apoptosis-inducing activity to that from a hybridoma cell line. These data provide essential information for the humanization and clinical application of the humanized HFE7A.