Background:

Avelumab is a fully human IgG1 anti-PD-L1 monoclonal antibody with potential antibody-dependent cell-mediated cytotoxicity.

Avelumab is a fully human IgG1 anti-PD-L1 monoclonal antibody with potential antibody-dependent cell-mediated cytotoxicity property. Avelumab increases NK-cell lysis 3.1-fold (P=0.01) in JHC7 cells relative to isotype control. When the cells are treated with IFN-γ, Avelumab markedly enhances NK-cell lysis relative to isotype control in the following cell lines: JHC7 (7.56-fold; P=0.001), UM-Chor1 (7.34-fold; P<0.001), U-CH2 (2.6 fold; P=0.008), MUG-Chor1 (8.38-fold; P=0.0016). Avelumab effectively increases antibody-dependent cell-mediated cytotoxicity (ADCC) of both the non-cancer stem cell (CSC) and CSC subpopulations to the same degree[1]. Results also demonstrate that the addition of Avelumab increases the frequency of antigen-specific multifunctional CD8+ T cells by more than fivefold, relative to the isotype control in CEFT-stimulated peripheral blood mononuclear cells (PBMCs)[2].

Measurement of individual tumors clearly shows a slowing of tumor growth in the Avelumab-treated mice. By day 36 post-tumor implantation, there is a significant (P<0.01) reduction in the average tumor volume of the Avelumab-treated mice. Reduction in MB49 tumor growth in the mice treated with Avelumab is durable and leads to a significant (P<0.05) improvement in percent survival. Avelumab treatment of 10 mice with bladder tumors results in complete tumor regression in 8 mice, confirmed by histopathology. However, in mice depleted of either CD4 or CD8 cells, Avelumab treatment is much less effective in controlling bladder tumor burden with tumor breakthrough occurring in a higher frequency in mice depleted of CD4 T cells[3].

[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. [2]. Grenga I, et al. A fully human IgG1 anti-PD-L1 MAb in an in vitro assay enhances antigen-specific T-cell responses. Clin Transl Immunology. 2016 May 20;5(5):e83. [3]. Vandeveer AJ, et al. Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. Cancer Immunol Res. 2016 May;4(5):452-62.