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Immune synapse
Learn what an immune synapse is and why it is relevant for cell therapy
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.
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.
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.
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.
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.
Solutions
Avidion
The next generation Cell Avidity platform
Ideal for cell therapy candidate screening and large characterization studies. Run up to 4 disposable 48-well cartridges a day for a total of 192 measurements with <80 min. hands-on time.
Avidigo
White glove Cell Avidity services
Full-service contract research from experimental design to data report based on Cell Avidity measurements at high throughput.
z-Movi
For small sized Cell Avidity studies
A fast and simple solution for single-sample Cell Avidity experiments. Run up to 20 measurements per day.
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We only show 4 and we have 6 types so the 2 older ones are hidden.
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The CAR Immune Synapse Interactome: How Membrane Organization Shapes CAR T–Tumor Cell Interactions
Webinar
September 14, 2026
01-01-20
Unlike conventional drugs, whose activity is shaped by binding to a single target, CAR T-cell (CART) engagement with tumor cells involves multiple receptors, adhesion molecules, and signaling proteins. These components are partially organized within cholesterol-rich membrane microdomains called lipid rafts, forming the CAR immune synapse (CARIS)—the interface through which a CART recognizes, attaches to, and kills a tumor cell.
To evaluate CARIS as a pharmacological interface, we compared CD28- and 4-1BB-CARTs, which exhibit distinct therapeutic profiles. The rapid antitumor activity of CD28-CARTs was associated with brief, dynamic synapses supporting rapid signaling and serial killing. Conversely, 4-1BB-CARTs formed longer, mechanically stable synapses consistent with their slower but sustained activity. Synapse strength was measured using z-Movi acoustic force microscopy.
Lipid rafts were enriched at CARIS. Attenuating membrane lipid raft cholesterol preferentially compromised 4-1BB CARIS mechanical stability, while predominantly impairing CD28 CARIS activation and cytolytic output. The molecular networks underlying these differences were mapped by integrating lipid-raft lipidomics, differential SILAC proteomics to distinguish CART-derived from tumor-derived components, and T-cell transcriptomics.
CD28-associated lipid rafts were enriched in diacylglycerol signaling components, PKCθ, small GTPases, Src-family kinases, and AKT/PI3K-proximal modules, supporting rapid signal-to-function coupling. Stomatin-family and flotillin scaffolds favored dynamic remodeling, while CD8-dominant transcriptional programs supported cytolytic degranulation. Engaged tumor cells displayed membrane-stress signatures consistent with late-stage senescence and apoptotic commitment.
In contrast, 4-1BB-associated lipid rafts were enriched in lysophosphatidic acid, an inhibitory lipid known to suppress CD8 effector functions while promoting integrin-dependent adhesion, consistent with the marked enrichment of integrins at CARIS, NF-κB and cytokine signaling components, and ERM scaffolds that couple lipid rafts to cortical actin, sustaining CARIS stability. Engaged tumor cells exhibited signatures of early apoptotic resistance, including damage-response and repair markers.
Together, these findings establish CARIS as a central determinant of CART function and therapeutic behavior. Mapping and manipulating its lipid–protein networks provide a platform for understanding CART pharmacodynamics and developing strategies to improve therapeutic efficacy.
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Enhancing efficacy against clear cell renal cell carcinoma through format-tuning of bispecific T cell engagers
Scientific update
January 29, 2025
01-01-20
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Cell Avidity: a key to accelerate IND filing in cell therapy drug development
Whitepaper
July 1, 2023
01-01-20
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Accelerate your cell engager discovery with high throughput measurements of Cell Avidity
Application note
June 1, 2023
01-01-20
T cells play a pivotal role in tumor immunosurveillance. Multispecific cell engagers (CEs) have been adopted in the field of immuno-oncology to redirect T cells toward cancer cells, thereby unleashing the anti-tumor potential of the patient’s immune system. CE-mediated cell binding induces T cell activation and the formation of an immunological synapse, which is a prerequisite for effective tumor cell lysis.
The strength of the initial binding events between a T cell and a tumor cell dictates the efficiency of the anti-tumor response. Assessing cell avidity, i.e. the total intercellular interaction strength between two cells, gives crucial insights into the efficacy of CEs as anti-tumor therapeutic agents.
Here, we deploy LUMICKS’ high throughput avidity measurement (HTAM) technology to measure CE-induced cell avidity in a high throughput manner. We demonstrate the assay performance characteristics, i.e. specificity, precision, and range, via CE titration experiments in the context of a Jurkat T cell model system. We find that the HTAM CA assay is suitable for candidate screening in high throughput, with high sensitivity and precision.
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Cell Therapy Case Study Collection
Brochure
September 8, 2025
01-01-20
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