Avelumab (anti-PD-L1) (Bavencio, MSB0010718C) is a fully human IgG1 monoclonal antibody that targets the protein programmed death-ligand 1 (PD-L1). Avelumab exhibits potential antibody-dependent cell-mediated cytotoxicity and is used for the treatment of
Avelumab (anti-PD-L1) (Bavencio, MSB0010718C) is a fully human IgG1 monoclonal antibody that targets the protein programmed death-ligand 1 (PD-L1). Avelumab exhibits potential antibody-dependent cell-mediated cytotoxicity and is used for the treatment of several kinds of carcinoma. MW=143.8 kDa.
Co-incubating chordoma cells with brachyury-specific CD8+ T cells results in significant upregulation of PD-L1 on the tumor cells, mediated by the CD8+ T cells' IFN-γ production, and increases sensitivity of chordoma cells to avelumab-mediated ADCC. Residential cancer stem cell subpopulations of chordoma cells are also killed by avelumab-mediated ADCC to the same degree as non-cancer stem cell populations. As a monotherapy for chordoma, avelumab may enable endogenous NK cells, while in combination with T-cell immunotherapy, such as a vaccine, avelumab may enhance NK-cell killing of chordoma cells via ADCC.[1]
An aggressive, bioluminescent orthotopic bladder cancer model, MB49 tumor cells transfected with luciferase (MB49luc) is used to study the antitumor effects of avelumab. MB49luc bladder tumors are highly positive for the expression of PD-L1 and avelumab administration induces significant (P<0.05) antitumor effects.[2]
[1] Rika Fujii, et al. Oncotarget. 2016 Jun 7;7(23):33498-511. [2] Amanda J Vandeveer, et al. Cancer Immunol Res. 2016 May;4(5):452-62.
Cell experiment: | To examine the relationship between a cancer stem cell (CSC) subpopulation and antibody-dependent cell-mediated cytotoxicity (ADCC) activity, UM-Chor1 cells are left untreated or treated with 50 ng/mL of IFN-γ for 24 h. Cells are then plated as targets at 50,000 cells/well in 6-well round-bottom culture plates and incubated with 2 μg/mL of Avelumab at room temperature for 30 min. NK cells are added at 2500,000 cells/well at an effector-to-target (E:T) ratio of 50:1. After 4 h, tumor cells are harvested and stained with antibodies for flow cytometry[1]. |
Animal experiment: | Female C57BL/6 mice are used in this study. Subcutaneous tumor injections are carried out by inoculating C57BL/6 mice with 1×105 MB49 parental cells on the right shaved flank. Tumor growth is measured with calipers and 8 days post-inoculation mice are assigned to treatment groups. Tumor-bearing mice are treated with Avelumab (400 μg per 100 μL) and injected i.p. three times, 3 days apart. Since Avelumab is a human IgG1, three injections have to be compressed within a 7 to 9 day window (i.e., days 9, 12, and 15 post-tumor inoculation) to avoid the onset of neutralizing mouse anti-human Ig[3]. |
参考文献: [1]. Fujii R, et al. Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab. Oncotarget. 2016 Jun 7;7(23):33498-511. | |
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