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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.
Technical note:
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Filter CA and show 4 Latest
This shows the most recent card of each resource type filtered on Business Unit CA.
Webinar, Scientific update, Whitepaper, Application note, Brochure.
We only show 4 and we have 6 types so the 2 older ones are hidden.
In design only 1 is shown, but the rest will be loaded when published.
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Avidity and functional characterization of CD19/BCMA dual-targeting CAR-T cell designs in NHL
Webinar
July 1, 2026
01-01-20
CD19-directed CAR-T therapy has achieved remarkable clinical outcomes in patients with relapsed or refractory non-Hodgkin lymphoma (NHL). Nevertheless, a significant proportion of patients develop primary resistance or relapse, often associated with CD19 antigen loss or downregulation. Given the co-expression of CD19 and BCMA in NHL, we hypothesized that dual antigen targeting could improve therapeutic durability and mitigate antigen escape. To address this, we developed a panel of CD19/BCMA dual-targeting CAR-T cells building on our academic platforms targeting CD19 (varnimcabtagene autoleucel, ARI0001) and BCMA (cesnicabtagene autoleucel, ARI0002h). Multiple strategies were explored, including pooled mono-targeted products, co-transduction with two lentiviral vectors, bicistronic constructs, and tandem/loop CAR designs incorporating dual binding domains within a single receptor. Functional activity and avidity were assessed across varying antigen expression conditions. We found that dual CAR-T cells generated through co-transduction consistently showed superior performance relative to single-target CD19 CAR-T cells and other dual-targeting formats, particularly in models with low CD19 expression. A first-in-human phase I clinical trial (CARTDBG-01; NCT06097455) is currently underway to evaluate the safety and efficacy of ARI0003 in NHL.
Related publication: Bachiller, M., Barceló-Genestar, N., Rodriguez-Garcia, A., Alserawan, L., Dobaño-López, C., Giménez-Alejandre, M., ... & Guedan, S. (2025). ARI0003: Co-transduced CD19/BCMA dual-targeting CAR-T cells for the treatment of non-Hodgkin lymphoma. Molecular Therapy, 33(1), 317-335. https://doi.org/10.1016/j.ymthe.2024.11.028
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Text Link
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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