Mixed Lymphocyte Reaction for novel cancer immunotherapy testing
10 / 18 / 2018
The immunological synapse that occurs between T lymphocytes and Dendritic cells (DCs) is a key component of an effective immune response and is controlled by a combination of stimulatory and inhibitory signals – also called immune checkpoints. As to trigger a better anti-tumor immune response, interventions through a fine-tuning of these control signals within the immunological synapse represent one of the most promising cancer immunotherapy strategies.
The immunological synapse that occurs between T lymphocytes and Dendritic cells (DCs) is a key component of an effective immune response and is controlled by a combination of stimulatory and inhibitory signals – also called immune checkpoints. As to trigger a better anti-tumor immune response, interventions through a fine-tuning of these control signals within the immunological synapse represent one of the most promising cancer immunotherapy strategies.
In order to investigate novel immunotherapeutics capable of enhancing DC-mediated T cell activation, Explicyte set up and validated a robust and high throughput human allogeneic mixed lymphocyte reaction (MLR) assay, which consists in a co-culture of CD4+ T cells (responder) with monocyte-derived DCs (stimulator) and in the HTRF-based quantitation of IFNγ, a relevant surrogate of T cell activation. Our assay is a well-suited system for biologics and small molecules assessment either as single agents and/or forcombination therapies, including e.g. immune checkpoint inhibitors, and can thus be ran in various types of studies spanning from screening to potency profiling and functional characterization of candidate compounds.
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Highlighting of robust and optimizable MLR response in different human allogeneic T-DC donor pairs.
(A) While displaying an expected response amplitude varying from a donor pair to another one, the MLR response is robust and is further optimized following PD1 blockade. Isolated peripheral blood monocyte-derived DCs from six human donors are mixed with CD4+ T cells each isolated from different donors. IFNγ levels released in the supernatants are measured after 72h using a specific HTRF-based specific kit.
(B) PD1/PDL1 blockade characterization in an allogeneic MLR assay. Isolated peripheral blood monocyte-derived DCs from a human donor are mixed with CD4+ T cells isolated from a second donor. IFNγ levels released in the supernatants are measured after 72h using a specific HTRF-based specific kit. Anti-PD1 (Nivolumab and Pembrolizumab) and anti-PDL1 (Atezolizumab) antibodies potentiate DC-mediated T cell activation as highlighted by IFNg increase in the MLR assay.
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