Generation, immunologic characterization and antitumor effects of human monoclonal antibodies for carcinoembryonic antigen.

摘要: We generated fully human mAbs (HmAbs) to carcinoembryonic antigen (CEA) using the KM mouse, which carries a chromosome 14 fragment containing entire Ig H chain loci and κ L segments in mouse genome. Forty-six hybridoma clones producing HmAbs CEA were thus obtained by fusing P3-U1 myeloma cells with splenocytes of mice immunized CEA. Among them, 22 produced that reacted but not 3 other CEA-related cell adhesion molecule (CEACAM) family members, CEACAM1, CEACAM6 CEACAM8. In 12 examined, 8 IgG4, 2 IgG3, 1 was IgG2, IgG1. The affinity constants for these comparable those previously prepared anti-CEA (MmAbs). BIAcore analyses revealed react epitopes defined MmAbs on domain N A1 or B1 CEA, respectively. presence complement vitro, tested showed substantial cytotoxicity, namely, 50–65%, against CEA-expressing tumor cells. With lymphokine-activated killer exhibited 40–65% Ab-dependent cell-mediated cytotoxicity Moreover, one induced significant inhibition growth when administered xenografted Considering their lack immunogenicity humans, CEA-specific may be useful immunotherapeutic approaches as well immunodiagnosis. © 2003 Wiley-Liss, Inc.