Accelerate your cell engager discovery
Determine avidity EC50 and binding kinetics of T cell engagers to quantify trimer formation across multiple dimensions in the cell-cell context.
Part of:
Why Cell Avidity?
Keeping up with the complexity of binding mechanisms
Many immunotherapies adapt to solve the field’s most pressing issues (an intricate balance between persistence, potency, and safety) by integrating multiple signaling mechanisms and engaging with more than one target in parallel (e.g., bi- and trispecific cell engagers). With that trend, the binding mechanisms between binder and target also complexify.
Molecular binding assays like tetramer binding and surface plasmon resonance (SPR) measure preconditions for binding, providing limited insights into actual cell binding. Focusing on isolated ligand-receptor interactions or abundance on a molecular level, they can miss the cellular context and often do not correlate well with functional outcomes.
Overcome these challenges with Cell Avidity:
- Generate direct, physiologically relevant measurements of binding in its full, dynamic complexity
- Understand the mechanism of action of your therapeutic products by revealing its complex binding dynamics
- Balance potency and safety by optimizing binding
Balancing pharmacokinetic benefits with cell avidity optimization for cell engager success
First-generation bispecific T cell engagers (BTEs) have shown promise in preclinical models but often suffer from a short plasma half-life due to their small size and absence of an Fc domain. Additionally, limited tumor retention can lower local therapeutic concentrations and impede efficacy. Cancer cells can even adapt and evade immune targeting through antigen heterogeneity and loss, threatening sustained responses. The immunosuppressive tumor microenvironment further hinders T cell function and promotes therapeutic resistance. To develop an effective strategy, any cell engager must overcome these barriers to achieve robust, consistent targeting and immune activation.
Case study
Enhancing efficacy against clear cell renal cell carcinoma through format-tuning of bispecific T cell engagers
A team led by David Weiner, PhD have examined how format-tuning bispecific T cell engagers (BTEs) boosts therapeutic efficacy against clear cell renal cell carcinoma (ccRCC). Using a novel persistent multivalent T cell engager (PMTE) to enhance cell avidity and tumor targeting, they tackle challenges like low plasma half-life, poor tumor retention, and antigen escape. Optimizing cell interactions through avidity-driven design offers a pathway to more effective, durable cancer therapies and renewed hope for advanced ccRCC patients.
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Binding correlated with in vivo tumor cell-killing efficacy. Comparing the three BTE formats shows a significant delay in tumor volume increase between BTE, PBTE and PMTE. Data adapted from O’Connell et al. (CC-BY-NC)
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Cell avidity curves represent the % of target cells bound with rising detachment force measured at 30 nM, 3 nM and 300 pM antibody concentration. Area-under-curve quantifications indicate the significant differences in cell avidity between PBTE and PMTE at relevant concentrations. Adapted from: O’Connell et al. (CC-BY-NC)
This study compared three BTE formats. Left: single-chain “BTE” with a tumor-targeting aCA9 linked to the T cell-targeting aCD3. Center: second-generation PBTE which reintroduces an Fc domain. Right: PMTE format which adds another tumor-targeting aCA9 part.
Dive into the publication
Format-tuning of in vivo-launched bispecific T cell engager enhances efficacy against renal cell carcinoma
O’Connell, R. P. et al.
January 1, 2024
https://jitc.bmj.com/content/12/6/e008733
Publication
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:
These cards are NOT components because they use the finsweet nested collection logic. To pull in the posible multiple people wo worked on it.
This type of 1-many relation is not supported native in Webflow.
Also this section is hidden when emtpy. To keep everything visible here, that is being done outside the webflow designer from within Slater.
These cards are NOT components because they use the finsweet nested collection logic. To pull in the posible multiple people wo worked on it.
This type of 1-many relation is not supported native in Webflow.
Also this section is hidden when emtpy. To keep everything visible here, that is being done outside the webflow designer from within Slater.
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