A comparison of the in vitro and in vivo activities of IgG and F(ab')2 fragments of a mixture of three monoclonal anti-Her-2 antibodies.

摘要: Purpose: We have demonstrated previously that a mixture of three anti-Her-2 monoclonal antibodies (MAbs) bind to different epitopes on the extracellular domain Her-2 expressed human breast cancer cell line has more potent antitumor activity than individual MAbs both in vitro and xenografted severe combined immunodeficient mice. Because Herceptin is Fc dependent, we determined whether this would also be case when these was used. Experimental Design: IgG highly purified F(ab′) 2 fragments were prepared evaluated for their ability induce death, inhibit vascular endothelial growth factor secretion, mediate antibody-dependent cellular cytotoxicity complement-mediated . They compared abilities regression large BT474 tumors Results: All >95% pure and, as expected, did not or complement-dependent The antiproliferative proapoptotic effects IgGs similar. In contrast, had significant vivo , whereas only marginally effective even at 5-fold higher doses offset shorter half-lives. Conclusions: These results confirm importance portion optimal demonstrate are inducing death requires Fc-mediated effector function activity.