Stromal platelet-derived growth factor receptor α (PDGFRα) provides a therapeutic target independent of tumor cell PDGFRα expression in lung cancer xenografts.

In lung cancer, platelet-derived growth factor receptor α (PDGFRα) is expressed frequently by tumor-associated stromal cells and by cancer cells in a subset of tumors. We sought to determine the effect of targeting stromal PDGFRα in preclinical lung tumor xenograft models (human tumor, mouse stroma). Effects of anti-human (IMC-3G3) and anti-mouse (1E10) PDGFRα monoclonal antibodies (mAb) on proliferation and PDGFRα signaling were evaluated in lung cancer cell lines and mouse fibroblasts.

Marked therapeutic efficacy of a novel polyethylene glycol-SN38 conjugate, EZN-2208, in xenograft models of B-cell non-Hodgkin's lymphoma.

Examination of the clinical utility of SN38 (10-hydroxy-7-ethyl-camptothecin), the active metabolite of CPT-11, has not been possible to date due to poor solubility of SN38. Here we evaluated the activity of EZN-2208, a water-soluble polyethyleneglycol-SN38 conjugate, in pre-clinical models of Burkitt's non-Hodgkin's lymphoma (NHL) (Raji and Daudi), and follicular NHL (DoHH2). In vitro, the IC50 of EZN-2208 ranged from 3-24 nM, which was 30- to 45-fold lower than CPT-11 or 2.

Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model.

Purpose: Clinical development of SN38, the active metabolite of camptothecin-11 (CPT-11), has been hampered due to its poor solubility. We have developed a novel polymer-drug conjugate, EZN-2208, made by linking SN38 with a multiarm polyethylene glycol via a glycine linker.

Experimental Design: The in vitro cytotoxicity of EZN-2208 was tested using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay.