Anti-Tumor Effects In vivo Sample Clauses

Anti-Tumor Effects In vivo. The anti-tumor activity of molecules that interfere with EphA3 activity suggest that both unconjugated and conjugated antibodies will have therapeutic effect in mouse models. The optimal form of an EphA3 targeted therapeutic will have to be determined. Work by Xxxxxxx et al has shown anti-tumor activity of a [***] antibody conjugate and a [***] IgG dimer in a human tumor xenograft model in the mouse. Brantley et al have shown anti-tumor activity of an EphA3-Fc fusion protein in a xenograft of the 4T1 mammary cell line. The EphA3-Fc protein was shown to reduce vascular density and tumor volume. EphA2-Fc fusion protein was also active in these types of models. Antibodies to EphA2 have been reported to show anti-tumor activity in animal models. EphA2 is expressed on tumor cells and tumor vasculature and EphA2-Fc protein inhibits tumor angiogenesis. The importance of EphA3 targeting of endothelial cells for anti-tumor activity needs to be investigated in addition to direct tumor cell effects. The development candidate will be expected to show anti-tumor activity in tumor xenograft models of EphA3 expressing and non-expressing human tumors. The indirect anti-tumor activity (against tumor cells not expressing EphA3) should be through tumor endothelial cell effects (angiogenesis).
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