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Background CD138 / syndecan-1 is a transmembrane heparan sulfate proteoglycan excerting different functions such as mediation of cell proliferation, cell migration and cell-matrix interactions, contributing to the tumor cell interaction with surrounding tissues. BT-062 is an immunoconjugate directed against CD138 based on ImmunoGen's TAP (targeted antibody payload) technology consisting of approximately 3.5 DM4 molecules per antibody linker via a hindered disulfide linker. The conjugate is inactive in blood plasma and the original killing potency of the drug is restored only after internalisation into the CD138-expressing target cell. Besides multiple myeloma, syndecan-1 overexpression has been detected in several solid tumor types such as in carcinomas of the pancreas, breast, prostate, colon, lung, endometrial ovarian, head and neck and bladder [3, 4]. Since BT-062 targets and kills CD138-positive multiple myeloma cells with high potency and specificity as previously demonstrated [1], preclinical studies were conducted to investigate the potential of BT-062 for the treatment of CD138 expressing solid tumors. References [1] Ikeda et al., 2009, Clin Cancer Res, 15(12): 4028-4037. [2] Chanan-Khan et al., ASH 2009. Poster [3] Saqi et al., 2005, Diagn Cytopathol., 33(2): 65-70. [4] Anttonen et al., 1999, Br J Cancer, 79(3-4):558-64. [5] Fiebig et al., 2001,Tumor models in Cancer Research. In Teicher BA: 113-137. • CD138 expression was analysed on several tumorigenic cell lines by BT-062, using flow cytometry • Patient-derived tumor tissue which had been directly transplanted from patients into mice (Oncotest GmbH, Freiburg, Germany) were screened for CD138 expression intensity and homogeneity by Immunohistochemistry (IHC). These primary human tumor xenotransplants retain most characteristics of the parental tumors including histology and response to standard anti-cancer drugs [5]. • Treatment of primary tumor xenografted mice with BT-062 Methods # 226 Results |
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