[A bispecific monoclonal antibody with versatile adaptor mediating different cytotoxicities].
Bispecific monoclonal antibody (bsMAb), secreted by hybrid-hybridoma, has an intact 1g molecule construction with dual antigen binding specificities. bsMAb has several advantages over conventional conjugate in tumor targeting therapy: (1) The damage to both antibody and tumoricidal agents due to chemical crosslinking can be avoided. (2) The antigen modulation can be decreased due to monovalence binding of bsMAb with target antigen. (3) The binding affinity between Fc fragment of bsMAb with heterogenous heavy chains and Fc receptor is decreased, so that nonspecific distribution and side effects can be reduced. (4) The bsMAb can pretarget to tumor site, increasing the T/NT ratio and cytotoxicity. In the present study, A bsMAb with versatile adaptor was designed. In this bsMAb, one arm could react with gastric cancer-associated antigen, and the other with a hapten TNP. The bsMAb could mediate different tumoricidal agents crosslinked to TNP. A variant hybridoma 3H11-HAT(s) secreting McAb against gastric cancer was fused with spleen cells of mice immunized with KLH-TNP. After screening and subcloning, 10 hybrid-hybridomas were obtained, which secreted antibodies against both gastric cancer target cells BGC823 and BSA-TNP. By using special bridge method, only hybrid-hybridomas 6A3 (gamma 2b, mu), and 1G7 (gamma 2b, gamma 2b) were confirmed to secrete bsMAb. Further experiments showed that the bsMAb 6A3 and 1G7 could mediate different cytotoxicities, for example, Ricin-TNP, MMC-HSA-TNP and ADM-BSA-TNP. This system is useful for evaluating different tumoricidal agents in bsMAb targeting therapy, and has potential value in clinics.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
L M
LM
Department of Biochemistry, Beijing Institute for Cancer Research.
Wan
W H
WH
Lu
L J
LJ
D000818:Animals; D000911:Antibodies, Monoclonal; D004317:Doxorubicin / Q000494:pharmacology; D006241:Haptens / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000494:pharmacology; D012276:Ricin / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000276:immunology; D013274:Stomach Neoplasms / Q000473:pathology; D014301:Trinitrobenzenes / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D006241:Haptens; D000922:Immunotoxins; D014301:Trinitrobenzenes; C038601:trinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D016685:Mitomycin; D004317:Doxorubicin; D012276:Ricin