Identification of a novel prostate tumor target, mindin/RG-1, for antibody-based radiotherapy of prostate cancer - PubMed (original) (raw)

. 2005 Sep 15;65(18):8397-405.

doi: 10.1158/0008-5472.CAN-05-1203.

Doug Schneider, Debra Hudson, Debbie Parkes, Jian-Ai Xuan, Alicia Newton, Pam Toy, Rick Lin, Rick Harkins, Bruno Alicke, Sandra Biroc, Peter J Kretschmer, Meredith Halks-Miller, Helmut Klocker, Ying Zhu, Brent Larsen, Ronald R Cobb, Peter Bringmann, Georg Roth, Jason S Lewis, Harald Dinter, Gordon Parry

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Identification of a novel prostate tumor target, mindin/RG-1, for antibody-based radiotherapy of prostate cancer

Renate Parry et al. Cancer Res. 2005.

Abstract

Gene expression analysis showed that a human mindin homologue, mindin/RG-1, is expressed selectively in prostate tissues and that its expression level is elevated in some prostate tumors. Mindin/RG-1 protein expression is maintained in >80% of prostate cancers metastatic to bone or lymph nodes as well as in locally recurrent tumors in androgen-unresponsive patients. In contrast, mindin/RG-1 expression in other normal tissues is significantly lower than that seen in the prostate. A fully human antibody, 19G9, was generated against mindin/RG-1 protein and was shown to accumulate at high abundance in LNCaP tumor xenografts. Conjugates of this antibody with the chelator CHX-A''-DTPA were generated and radiolabeled with either 111In, 90Y, or 86Y. Small animal positron emission tomography imaging with the 86Y-radiolabeled conjugate showed very specific accumulation of the antibody in LNCaP tumor xenografts with clear tumor delineation apparent at 4 hours. The therapeutic efficacy of [90Y]-CHX-A''-DTPA-19G9 was evaluated in mice bearing LNCaP xenografts. A dose-finding study identified a nontoxic therapeutic dose to be approximately 75 microCi. Significant antitumor effects were seen with a single administration of radiolabeled antibody to animals bearing 200 to 400 mm3 tumors. Inhibition of tumor growth was observed in all treated animals over a 49-day period. At 49 days posttreatment, slow tumor growth recurred but this could be prevented for an additional 40-day period by a second administration of a 75 microCi dose at day 49. We conclude that [90Y]-CHX-A''-DTPA-19G9 is a novel antibody conjugate that has considerable promise for therapy of metastatic prostate cancer in androgen-unresponsive patients.

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