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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.

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.
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.
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Avidigo

White glove Cell Avidity services

Full-service contract research from experimental design to data report based on Cell Avidity measurements at high throughput.
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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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Relevant resources

Learn as much as you can by reading up on our application notes or marathoning our webinars.

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Rational CAR design: Integrating affinity and tonic signaling
Rational CAR design: Integrating affinity and tonic signaling
Webinar
September 24, 2025
01-01-20

The success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies has not yet translated into long-term elimination of solid tumors, indicating the need for adequate tuning of CAR T cell functionality. The CAR binding moiety is the critical trigger for CAR T cell signaling. CAR binding affinity alone does not determine T cell effector functions. In a panel of anti-Her2 CARs covering a 4-log affinity range, we observed that rather high affinity and cell avidity above the minimum threshold, combined with elevated tonic signaling, produce adequate T cell capacity for expansion and tumor control. The same scFv mutations increased both antigen-specific affinity, cell avidity, and antigen-independent tonic signaling; above a minimum threshold, raise in affinity translated into cell avidity in a non-linear fashion. In this case, replacement by amino acids of higher hydrophobicity within the scFv coincidentally augmented affinity, non-specific binding, spontaneous CAR clustering, and tonic signaling, all together relating to T cell functionality in an integrated fashion. Data highlight the mechanistic complexity of CAR signaling and suggest inclusion of additional variables, for example, hydrophobic interactions, into the equation when determining the CAR’s antigen-specific and tonic signaling capacities.

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Enhancing efficacy against clear cell renal cell carcinoma through format-tuning of bispecific T cell engagers
Enhancing efficacy against clear cell renal cell carcinoma through format-tuning of bispecific T cell engagers
Scientific update
January 29, 2025
01-01-20

Cell Avidity: a key to accelerate IND filing in cell therapy drug development
Cell Avidity: a key to accelerate IND filing in cell therapy drug development
Whitepaper
July 1, 2023
01-01-20

Accelerate your cell engager discovery with high throughput measurements of Cell Avidity
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.

Cell Therapy Case Study Collection
Cell Therapy Case Study Collection
Brochure
September 8, 2025
01-01-20

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