Recombinant monoclonal antibody to TWEAK receptor. Enavatuzumab is a humanized monoclonal antibody designed for the treatment of cancers.
Figure 1 Enavatuzumab inhibited the growth of primary tumors and metastases in xenograft models of breast cancer.
Established MCF7 (a) and HCC70 (b) tumors were treated with enavatuzumab or a human IgG1 control antibody at 10 mg/kg three times per week, with 10 animals in each dosing group. Tumor volumes were measured on each dosing day; points, mean; bars, SEM. Differences in tumor volumes between the enavatuzumab and control treated groups were significant (p \ 0.001) in both models. c-e Established MB231 variant tumors were treated with enavatuzumab or a human IgG1.
Chao, D. T., Su, M., Tanlimco, S., Sho, M., Choi, D., Fox, M.,... & Zhang, Y. (2013). Expression of TweakR in breast cancer and preclinical activity of enavatuzumab, a humanized anti-TweakR mAb. Journal of cancer research and clinical oncology, 139(2), 315-325.
Figure 2 Enavatuzumab enhanced the antitumor activity of gemcitabine and navelbine in a triple-negative model of breast cancer.
Established MB231 variant xenograft tumors were treated with enavatuzumab at 1 mg/kg thrice weekly, alone or in combination with gemcitabine at 30 mg/kg (a) or vinorelbine at 5 mg/kg (b) twice weekly, with 7 mice in each dosing group.
Chao, D. T., Su, M., Tanlimco, S., Sho, M., Choi, D., Fox, M.,... & Zhang, Y. (2013). Expression of TweakR in breast cancer and preclinical activity of enavatuzumab, a humanized anti-TweakR mAb. Journal of cancer research and clinical oncology, 139(2), 315-325.
Figure 3 Growth inhibition of breast cancer cell lines by enavatuzumab and synergy of inhibition when combined with trastuzumab.
a-d BT549 (a), HCC38 (b), MB231 variant (c), and HCC70 (d) breast cancer cells were incubated with soluble enavatuzumab or human IgG1 control antibody in the presence (x, D) or absence (filled triangle, not shown) of cross-linking antibody, or immobilized enavatuzumab or control antibody (filled square, not shown) for 5-10 days. Relative viability was calculated by dividing the viability of treated cells by that of untreated cells. Representative data are shown here (point, mean of triplicate wells; bars, SEM).
Chao, D. T., Su, M., Tanlimco, S., Sho, M., Choi, D., Fox, M.,... & Zhang, Y. (2013). Expression of TweakR in breast cancer and preclinical activity of enavatuzumab, a humanized anti-TweakR mAb. Journal of cancer research and clinical oncology, 139(2), 315-325.
Figure 4 Enavatuzumab induces effector cell activation and tumor cell killing in vitro.
(a) Human PBMCs were coincubated with Cr-51labeled tumor target cells with E : T at 40 : 1 for 4 hr in the presence of enavatuzumab. Tumor cell cytotoxicity was calculated based on Cr-51 released into culture supernatant. Antibody-independent cell cytotoxicity (AICC) was also calculated. Experiments were performed with PBMCs from 4 donors. Representative data collected from one donor are shown. (b) Human PBMCs, cultured either alone or with indicated tumor cells at a 10 : 1 ratio, were treated with enavatuzumab or a control antibody. 24 hrs later, CD54 and CD16 levels were assessed on both monocytes (Mono) and NK cells by flow cytometry. Experiments were performed with PBMCs from 8 donors. Representative data collected from one donor were shown. (c) PBMCs were cultured with SN12C cells at the indicated ratios for 24 hr in the presence of enavatuzumab or a control antibody, after which CD69 was assessed on NK cells by flow cytometry (left) or cytokeratin18 levels were quantified in cell supernatants as a measure of tumor cell cytotoxicity (right). Enavatuzumab treatment increased CD69 levels at all E : T ratios tested (representative data from 4 donors) but significantly stimulated cytotoxicity only at 10 : 1 and 25 : 1 ratios (n = 4, ∗p < 0 05).
Ye, S., Fox, M. I., Belmar, N. A., Sho, M., Chao, D. T., Choi, D.,... & Culp, P. A. (2017). Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells. Journal of immunology research, 2017.
Figure 5 Enavatuzumab showed diverse antitumor activities on different xenograft tumors.
(a) Enavatuzumab or two variants of enavatuzumab containing mutations in the Fc region were incubated with mouse splenocytes. Binding to CD11bhigh cells was measured by FACS. ADCC activities of enavatuzumab and its Fc mutant variants were evaluated by Cr-51 release with H520-TweakR cells as targets and mouse splenocytes as effectors at a ratio of 1 : 40. (b) Established SN12C tumors were treated with enavatuzumab, a variant of enavatuzumab with no FcγR binding, or a control antibody (10mg/kg) three times a week for a total of seven doses, with dosing days indicated by the arrows above the graph. Dosing groups contained 10 animals each. Treatment with enavatuzumab, but not the Fc mutant, resulted in significant tumor growth inhibition on days 24–36 (p < 0 05). A375 tumors were similarly administered with nine doses of enavatuzumab, an Fc mutant variant, or a control antibody. Dosing groups contained 8 animals each, and significant growth inhibition was observed with both enavatuzumab and the Fc mutant on days 21–37 (p < 0 05). HCT116 and DLD-1 xenograft tumors were treated with enavatuzumab or a control antibody for nine or six doses (n = 8 or 10). Enavatuzumab treatment resulted in no tumor growth inhibition in either models.
Ye, S., Fox, M. I., Belmar, N. A., Sho, M., Chao, D. T., Choi, D.,... & Culp, P. A. (2017). Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells. Journal of immunology research, 2017.
Figure 6 Enavatuzumab treatment results in increased infiltration of CD45+ cells into tumors sensitive to antibody treatment.
Established xenograft tumors were treated with enavatuzumab or a control antibody (a) or Fc mutants (b) on day 0 and day 2 or 3, and the tumors were harvested on day 4 for immunohistochemical staining for mouse CD45.
Ye, S., Fox, M. I., Belmar, N. A., Sho, M., Chao, D. T., Choi, D.,... & Culp, P. A. (2017). Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells. Journal of immunology research, 2017.
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Afuco™ Anti-TNFSF12 ADCC Recombinant Antibody (Enavatuzumab), ADCC EnhancedThis product is an ADCC enhanced antibody produced by our Afuco™ platform. Recombinant monoclonal antibody to TWEAK receptor. Enavatuzumab is a humanized monoclonal antibody designed for the treatment of cancers.
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(Creative Biolabs Cat# TAB-178, RRID: AB_3111851)
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