Mixed Lymphocyte Reactions (MLR’s) are an important tool for assessing the bioactivity of a therapeutic on the adaptive immune system. MLR’s are an in-vitro cell-based assay with a wide variety of uses, from immunogenicity evaluations to potency. Xeno Diagnostics specializes in performing MLR’s for clients at all phases of drug development.
Mixed Lymphocyte Reaction is an in-vitro cell-based assay that replicates an adaptive immune response. The MLR uses lymphocytes (T-cells and B-cells) along with antigen presenting cells (monocytes, dendritic cells, and macrophages) to produce a cell-mediated immune response.
Cell mediated responses are caused by the presentation of a foreign antigen to T-cells, which then produce an adaptive response. The antigens are presented to T-cells by “antigen presenting cells” (APCs).
The MLR induces an adaptive immune response by one of two mechanisms:
An adaptive immune response is a delayed reaction as the body generates a targeted response to a pathogen; as opposed to an innate response which acts acutely. The adaptive response takes a longer time because lymphocytes (like T-cells and B-cells) must first recognize the new pathogen, and then develop a specific response by producing antibodies, coordinating other immune cells, and attacking the pathogen. By the end of this process, memory cells are formed. These cells can recognize that pathogen in the future to provide quicker and more effective responses.
MLRs have two main variables – cell type and cell source:
Therefore, there are several combinations that can be used to produce different effects:
Yes, in addition cell to source and cell types, there are also cell treatments. When performing an allogeneic PBMC reaction using PBMCs from two dissimilar individuals, both PBMCs populations have the ability to react. One of the populations is treated in order to arrest its response (proliferation), therefore it can only function as a stimulator for the other PBMC population.
Allogeneic MLR options:
Understanding how a therapeutic product (drug, device, tissue, therapy, etc.) effects our adaptive immune response is critically important for the safety of the potential patients. Because the MLR is used to produce in-vitro cell-mediated adaptive immune responses, it is a useful tool for assessing a products safety profile, understanding its mechanism of action, or measuring its efficacy.
MLRs can be used in the following scenarios:
Because the MLR is a tool used to measure in-vitro cell-mediated adaptive immune responses, it has a wide variety of applications where biological activity of a product or therapy needs to be considered. At Xeno Diagnostics our clients span a wide range of fields including:
There are three main responses to measure: viability, proliferation, and cytokine release. These can be measured in a variety of ways, from colorimetric ELISAs to Flow Cytometry.
Yes, flow cytometry is a powerful tool to measure cellular responses for the MLR. It allows for precise single cell measurements that can be performed on cell subsets (e.g. T-cells); it is also beneficial for monitoring changes in a product, if the product is a cellular therapy. Flow Cytometry can be used to measure:
Because there are many options for MLR format (allo, auto, 1-way, 2-way, PBMC or DC/T-cell) and a variety of readouts, the design must be carefully considered to produce the most mechanistically appropriate and relevant information for the intended use.
Xeno Diagnostics excels in designing bespoke MLRs for our clients to fit their needs. We consider the clients intended purpose, check the compatibility of their product, and factor in their regulatory needs to deliver a fit-for-purpose assay on time, in budget, all with publication quality results.
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