Publication Date:
2012-11-16
Description:
Abstract 2974 Daratumumab (DARA) is a human CD38 monoclonal antibody with broad-spectrum killing activity. DARA is in clinical development for multiple myeloma (MM) and has potential in other hematological tumors on which CD38 is expressed. In these clinical studies the adverse events have been manageable and marked reductions in paraprotein and bone marrow plasma cells have been observed. The killing activity of DARA on CD38-expressing tumor cells has previously been mainly attributed to complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). In this study we explored whether DARA could also kill CD38-positive cells via induction of apoptosis after immobilization of DARA via Fc receptors (FcRs) in vitro. To this end, target cells were co-incubated in vitro with hFcgRI-expressing cells, lacking ADCC activity, in the absence or presence of DARA. Apoptosis was measured in flow cytometry for annexin-V/7AAD positivity. Treatment of the Burkitt's lymphoma cell line Ramos with DARA in combination with hFcgRI-expressing cells, led to a significant enhancement of annexin–V/7AAD positive cells (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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