Recombinant monoclonal antibody to TRAIL-R2. Lexatumumab (also known as ETR2-ST01) is an experimental agonistic human monoclonal antibody against TRAIL-R2 (DR5, APO-2) undergoing clinical trials for the treatment of cancer.
Figure 1 Cleaved caspase 8 was associated with DR4 or DR5 in relation to mapatumumab or lexatumumab sensitivity.
Immunoprecipitation assays of mapatumumab (Mapa) or lexatumumab (Lexa) were performed in LP1, MDN, NCI-H929 cells. Cells (20 x 106) were incubated with or without (control) 10ug/ml of mapatumumab (45min) or lexatumumab (90 min) at 37°C in RPMI1640 containing 5% FCS. For NCIH929, cells were pretreated 2h with 2.5uM nutlin3a (N) before addition of lexatumumab. The lysates were immunoprecipitated with a mix of proteins A and G (2 mg of lysate proteins were immunoprecipitated in each assay). For untreated cells, IP was performed after addition of mapatumumab or lexatumumab to the lysates. The immunoprecipitates were analyzed for the presence of the indicated proteins by immunoblot analysis. Input: lysates of untreated or treated cells, Ct IP: immunoprecipitation of control lysates (untreated cells), IP: immunoprecipitation of lysates obtained from cells treated with mapatumumab or lexatumumab. * indicates heavy chain of mapatumumab or lexatumumab.
Surget, S., Chiron, D., Gomez-Bougie, P., Descamps, G., Ménoret, E., Bataille, R., ... & Pellat-Deceunynck, C. (2012). Cell death via DR5, but not DR4, is regulated by p53 in myeloma cells. Cancer research, canres-0487.
Figure 2 TGFβ1 inhibits apoptotic signaling of TRAIL-R1.
Cells were treated for 24 h with Mapatumumab (10μg/ml, Mapa), Lexatumumab (10μg/ml, Lexa), with or without pre-incubation with TGFβ1 (10 ng/ml for 72 h). Cell death was determined by PI-staining followed byflow cytometric analysis. (A) or by measurements of ATP content using the commercial CellTiter-Glo Luminescent Cell Viability Assay (B). Induction ratio shown in (A) (Mapa or Lexa treatment/respective control) is indicated below the histograms as fold of induction. Data depicted in A) and B) are shown as mean ± SEM of three independent experiments. *pb0.05, n.s. non-significant. (C) Cells were treated for 24 h with Mapa (10μg/ml), Lexa (10μg/ml), or with TRAIL (50 ng/ml) with or without pre-incubation with TGFβ1 (10 ng/ml for 72 h). Analysis of the apoptotic signaling cascade was performed on whole cell lysates by Western blot using antibodies against caspase 8, Bid and caspase 3. For the control of the gel loading,β-actin levels were determined in parallel.
Radke, D. I., Ungefroren, H., Helm, O., Voigt, S., Alp, G., Braun, H., ... & Kalthoff, H. (2016). Negative control of TRAIL-R1 signaling by transforming growth factor β1 in pancreatic tumor cells involves Smad-dependent down regulation of TRAIL-R1. Cellular signalling, 28(11), 1652-1662.
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Afuco™ Anti-TNFRSF10B ADCC Recombinant Antibody (Lexatumumab), ADCC EnhancedThis product is an ADCC enhanced antibody produced by our Afuco™ platform. Recombinant monoclonal antibody to TRAIL-R2. Lexatumumab (also known as ETR2-ST01) is an experimental agonistic human monoclonal antibody against TRAIL-R2 (DR5, APO-2) undergoing clinical trials for the treatment of cancer.
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(Creative Biolabs Cat# TAB-195, RRID: AB_3111865)
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