Key highlights:
- T cell avidity with tri-specific and bi-specific cell engagers quantified under physiological shear forces
- Avidity profiling reveals mechanistic differences invisible to conventional cytotoxicity assays
- Direct, side-by-side comparison of novel and competitor cell engager performance against melanoma cell lines
- Paired avidity and functional data enabling confident, mechanism-driven cell engager selection
The challenge
Etcembly is a biotechnology company using advanced machine learning and AI to discover, design, and optimise next-generation immunotherapies. Their pipeline includes novel tri-specific and bi-specific T cell engagers (TCEs) engineered to redirect T cells to recognise and eliminate cancer cells with greater precision and potency.
During preclinical development, cytotoxicity assays comparing Etcembly’s constructs against an existing competitor cell engager produced inconclusive results. Standard endpoint assays lacked the resolution to assess T cell engager target engagement under physiologically relevant conditions, leaving the team without the mechanistic clarity needed to confidently advance their programme against melanoma.
Our Approach
We applied our avidity-based microfluidic platform to directly measure T cell engagement with tumour targets under tightly controlled shear forces designed to reflect physiological flow conditions. Rather than relying on endpoint readouts alone, our approach quantified the total binding strength driving T cell–cancer cell interactions, capturing contributions from both cell engager-mediated binding and native T cell receptor engagement.
This enabled a rigorous, head-to-head avidity comparison across all constructs tested, run alongside matched cytotoxicity assays to provide a complete mechanistic and functional picture.
- T cell avidity quantified under physiologically relevant, controlled flow conditions
- Total binding strength measured across tri-specific, bi-specific, and competitor cell engagers
- Parallel functional validation through matched cytotoxicity assays
- Mechanism-of-action data enabling direct, like-for-like construct comparison
under force
melanoma target cell line
Our Approach
We applied our avidity-based microfluidic platform to directly measure T cell engagement with tumour targets under tightly controlled shear forces designed to reflect physiological flow conditions. Rather than relying on endpoint readouts alone, our approach quantified the total binding strength driving T cell–cancer cell interactions, capturing contributions from both cell engager-mediated binding and native T cell receptor engagement.
This enabled a rigorous, head-to-head avidity comparison across all constructs tested, run alongside matched cytotoxicity assays to provide a complete mechanistic and functional picture.
- T cell avidity quantified under physiologically relevant, controlled flow conditions
- Total binding strength measured across tri-specific, bi-specific, and competitor cell engagers
- Parallel functional validation through matched cytotoxicity assays
- Mechanism-of-action data enabling direct, like-for-like construct comparison
head-to-head under force
melanoma target cell line
Key Outcomes
Avidity profiling delivered a clear, rank-ordered picture of cell engager performance that cytotoxicity assays alone could not provide, revealing critical differences in T cell binding strength across all constructs tested.
Most strikingly, avidity data exposed a significant discrepancy between functional and mechanistic readouts for one construct, highlighting a layer of biological insight that standard assays routinely miss and that will have important consequences for in vivo efficacy.
Avigen approached our project with strong attention to detail and scientific integrity. Their careful optimisation of difficult assay conditions ensured in reliable, robust data that we could trust. The avidity readouts holistically captured meaningful aspects of functional immune–target engagement that was previously difficult to evaluate, adding a new layer of validation to our preclinical R&D. Interactions with the team were consistently positive and enjoyable. I would strongly recommend the team and their platform.


