IMPROVEMENT OF THERAPEUTIC EFFECT BY USING FAB' FRAGMENT IN THE TREATMENT OF CARCINOEMBRYONIC ANTIGEN-POSITIVE HUMAN SOLID TUMORS WITH ADRIAMYCIN-ENTRAPPED IMMUNOLIPOSOMES

To improve the therapeutic efficiency adriamycin entrapped in antibody -conjugated liposomes, Fab' fragment was used instead of the whole ant ibody molecule. The murine monoclonal antibody, 21B2, against human ca rcinoembryonic antigen (CEA) was digested with pepsin, and the thiol r esidue of intra-heavy chain produced by reduction of F(ab')(2) with di thiothreitol was conjugated to;liposomes containing adriamycin. The ti ssue distribution of adriamycin delivered with these liposomes was stu died in BALB/c nu/nu female mice bearing CEA-positive human gastric ca ncer strain MKN-45. An increase in delivery of adriamycin to the tumor was observed in the mice given liposomes with Fab' fragment as compar ed to those given liposomes with whole antibody. However, the preferen tial distribution of adriamycin in liposomes to the reticuloendothelia l cells remained the same regardless of the use of Fab' fragment. For investigation of in vivo therapeutic effect, three i.v. injections of free adriamycin or adriamycin in liposomes equivalent to 5 mg/kg were given, and adriamycin in Fab' fragment-conjugated liposomes was found most effective in the inhibition of tumor growth. This was confirmed i n terms of actual tumor weights excised and CEA concentration in the b lood, as well as by pathological observations. The advantages of using Fab' fragment instead of whole antibody are discussed.