In der Zeitschrift Blood ist von der weltweit führenden Arbeitsgruppe um K. Anderson/Boston ein interessanter Artikel über den Biotest-BT-062 (noch in muriner Form, unten bezeichnet als B-B4) veröffentlicht worden: Blood. 2004 Dec 1;104(12):3688-96. Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138+ multiple myeloma cells. Tassone P, Goldmacher VS, Neri P, Gozzini A, Shammas MA, Whiteman KR, Hylander-Gans LL, Carrasco DR, Hideshima T, Shringarpure R, Shi J, Allam CK, Wijdenes J, Venuta S, Munshi NC, Anderson KC. Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. We tested the in vitro and in vivo antitumor activity of the maytansinoid DM1 (N(2`)-deacetyl-N(2`)-(3-mercapto-1-oxopropyl)-maytansine), a potent antimicrotubule agent, covalently linked to the murine monoclonal antibody (mAb) B-B4 targeting syndecan-1 (CD138). We evaluated the in vitro activity of B-B4-DM1 against a panel of CD138(+) and CD138(-) cell lines, as well as CD138(+) patient multiple myeloma (MM) cells. Treatment with B-B4-DM1 selectively decreased growth and survival of MM cell lines, patient MM cells, and MM cells adherent to bone marrow stromal cells. We further examined the activity of B-B4-DM1 in 3 human MM models in mice: (1) severe combined immunodeficient (SCID) mice bearing subcutaneous xenografts; (2) SCID mice bearing green fluorescent protein-positive (GFP(+)) xenografts; and (3) SCID mice implanted with human fetal bone (SCID-hu) and subsequently injected with patient MM cells. Tumor regression and inhibition of tumor growth, improvement in overall survival, and reduction in levels of circulating human paraprotein were observed in mice treated with B-B4-DM1. Although immunohistochemical analysis demonstrates restricted CD138 expression in human tissues, the lack of B-B4 reactivity with mouse tissues precludes evaluation of its toxicity in these models. In conclusion, B-B4-DM1 is a potent anti-MM agent that kills cells in an antigen-dependent manner in vitro and mediates in vivo antitumor activity at doses that are well tolerated, providing the rationale for clinical trials of this immunoconjugate in MM. |
|
aus der Diskussion: | monoklonaler Antikörper mit Milliardenpotential von Biotest |
Autor (Datum des Eintrages): | Joschka Schröder (27.07.05 16:46:32) |
Beitrag: | 150 von 151 (ID:17364535) |
Alle Angaben ohne Gewähr © wallstreetONLINE |