Supplementary Table S3 from Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake

Supplementary Fig. S2 from Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake

Supplementary Fig. S1 from Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake

Abstract The insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II), which both signal through IGF-I receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-II binding and by inducing cell surface receptor down-regulation via internalization and degradation, with the extracellular and intracellular domains of IGF-IR being differentially affected by the proteasomal and lysosomal inhibitors. In vitro, h10H5 exhibits antiproliferative effects on cancer cell lines. In vivo, h10H5 shows single-agent antitumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models and even greater efficacy in combination with the chemotherapeutic agent docetaxel or an anti–vascular endothelial growth factor antibody. Antitumor activity of h10H5 is associated with decreased AKT activation and glucose uptake and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors and furthermore illustrate a new method of monitoring its activity noninvasively in vivo via 2-fluoro-2-deoxy-d-glucose-positron emission tomography imaging. [Mol Cancer Ther 2008;7(9):2599–608]

4468 Highly restricted expression patterns for cell surface antigens make them ideal candidates for targeted delivery of cytotoxic agents by specific monoclonal antibodies (′armed′ antibodies). STEAP1, six transmembrane epithelial antigen of the prostate, is one such antigen whose expression is highly localized to the prostate with minimal expression in other normal tissues. An antibody generated against the extracellular epitopes of STEAP1 recognizes STEAP1 on the cell surface of prostate cancer cell lines. This antibody, when armed with the auristatin microtubule destabilizing agents MMAE or MMAF, demonstrated potent efficacy in multiple established mouse xenograft models derived from prostate cancer cell lines or from patient derived prostate models. These results suggest that armed STEAP1 antibodies may be a promising therapeutic for the treatment of prostate cancer.

A thin foil electron microscope specimen containing precipitates may be etched after normal examination so that the intensity of the diffraction patterns from the precipitates is enhanced relative to the standardizing pattern from the matrix. It is thus often possible to examine internal defect structures and to determine accurately the interplanar spacings of the precipitates from the same specimen without having to prepare a separate extraction replica.