Monoclonal antibodies (MAbs) that interfere with checkpoint molecules are being 
investigated for the treatment of infectious diseases and cancer, with the aim 
of enhancing the function of an impaired immune system. Avelumab (MSB0010718C) 
is a fully human IgG1 MAb targeting programmed death-ligand 1 (PD-L1), which 
differs from other checkpoint-blocking antibodies in its ability to mediate 
antibody-dependent cell-mediated cytotoxicity. These studies were conducted to 
define whether avelumab could enhance the detection of antigen-specific immune 
response in in vitro assays. Peripheral blood mononuclear cells from 17 healthy 
donors were stimulated in vitro, with and without avelumab, with peptide pools 
encoding for cytomegalovirus, Epstein-Barr virus, influenza and tetanus toxin or 
the negative peptide control encoding for human leukocyte antigen. These studies 
show for the first time that the addition of avelumab to an antigen-specific IVS 
assay (a) increased the frequency of activated antigen-specific CD8(+) T 
lymphocytes, and did so to a greater extent than that seen with commercially 
available PD-L1-blocking antibodies, (b) reduced CD4(+) T-cell proliferation and 
(c) induced a switch in the production of Th2 to Th1 cytokines. Moreover, there 
was an inverse correlation between the enhancement of CD8(+) T-cell activation 
and reduction in CD4(+) T-cell proliferation induced by avelumab. These findings 
provide the rationale for the use of avelumab anti-PD-L1 in in vitro assays to 
monitor patient immune responses to immunotherapies.