What is an immune synapse and why is it relevant for cell therapy?
An immunological synapse is an interface between an antigen-presenting cell or a target cell and a lymphocyte or a natural killer cell, which is formed in a highly stable, organized manner. The immunological synapse is composed of all intercellular interactions between the interacting pair, including TCR clustering, checkpoint or costimulatory receptor binding, cell-cell adhesion proteins, and even orientations and valencies (Figure 1).
Proper formation of the immunological synapse between a cancer cell and an effector cell is required to initiate immune cell activation, achieve sustained proliferation, and increase cytokine secretion against the cancer cells. The organization of the T cell receptor (TCR) and the molecules present at the binding site impact how the immune cell functions, thus investigating the synaptic structure helps researchers to gain greater insights into the mechanism of action and better predict immunotherapy efficacy.
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Immunological synapse formation is triggered by TCR engagement. A bullseye structure is displayed at a TCR-mediated immunological synapse (left) and bsAb-mediated immunological synapse (right), while a nonclassical structure is formed in a CAR-mediated immunological synapse (middle). The functional consequence of the CAR-mediated immunological synapse is rapid signaling and expeditious cytotoxicity on tumor cells.
Prof. Hinrich Abken
University of Regensburg
“We expect to gain greater insight into the mechanism of CAR mediated tumor cell recognition and into the selection of the most potent CAR for clinical application.”
Investigating the immunological synapse can help predict cell therapy efficacy
The purpose of creating artificial construct engraftment strategies using TCR T cells, CAR T cells, and bispecific antibodies is to redirect the immune cells. However, to properly achieve this, scientists need to get a proper understanding of the molecular mechanisms that take place at the cell-cell interface between cancer and immune cells during immune cell activation. The structural or procedural differences in CAR-mediated and bsAb–mediated immunological synapse from the conventional TCR-mediated immunological synapse will likely alter the nature of the resulting signaling and the eventual therapeutic T cell responses. Therefore, looking into the binding events across the immunological synapse is a crucial step to accelerate cell therapy development.
A tool to measure the total intercellular binding strength beyond the single-receptor interactions between cancer cells and immune cells across the immunological synapse is called cell avidity analysis. Incorporating cell avidity not only provides insights into the biological complexity that is inherently linked to the immune cell function, but also helps researchers to identify the best immune cell candidates at an early stage. This early selection can improve the clinical success rate, and reduce costs and save time by reducing the use of in vivo mouse models.
Our solution
The z-Movi® Cell Avidity Analyzer is a solution for researchers to determine cell avidity, which has been notoriously difficult to measure until now. Through avidity measurements, the z-Movi can help researchers investigate cell interaction properties that correspond to immune cell response in a predictive, reproducible, and fast manner. All this at a high-throughput and single-cell level, without compromising cell viability.
Being able to measure these interactions provides researchers valuable information and enables them to select best candidates at an early stage. This informed selection from the start can improve their success rate dramatically.
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