Mechanism of Antitumor Activity in Mice for Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies with Different Isotypes

摘要: In previous studies of monoclonal antibodies (mAbs) against the receptor for epidermal growth factor (EGF) both 528 IgG2a and 225 IgG1 were shown to inhibit A431 cell xenografts in athymic mice. The antitumor activities two mAbs similar and, although they differ their isotypes, share many properties. bind EGF receptors with identical affinities, compete binding receptors, down regulate identically, block EGF-induced activation tyrosine protein kinase activity a comparable degree, changes proliferation cultured cells. These similarities physiological effects permit direct comparison mechanisms action isotypes. We examined vitro cytotoxicity cells, using mAbs. IgG2a, but not IgG1, demonstrated partial complement-mediated by 51Cr release assay inhibition was cytotoxic cells presence activated peritoneal macrophages, as incorporated [3H]thymidine. Neither mAb showed any significant nonadherent spleen which contain K-cells. results experiments suggested that could be mediated macrophages. This verified vivo s.c. tumor inocula containing macrophages enhancement animals treated i.p. twice weekly 3 weeks suboptimal doses IgG2a. observed when used same procedure. these suggest immune involving or complement contribute anti-EGF isotype, isotype. observation confirms findings others who other model systems. 225, possibly 528, may prevent human altering functions rather than mechanisms.