Are you developing multispecifics? This case study walks through how we profile a bispecific T-cell engager end to end — efficacy, mechanism, and cytokine-release liability — using tarlatamab, a CD3×DLL3 engager for small-cell lung cancer, as the worked example.
We start on DLL3-positive small-cell lung cancer cells (SHP77) against a DLL3-negative NSCLC control (A549), confirm target expression by flow cytometry, then measure immune-cell-mediated killing in dose-response format. From there, the study characterizes the anti-tumor immune response and asks a question functional readouts alone can’t answer: what is the molecule’s cytokine-release liability, and which cells drive it?
Inside the case study:
- Specificity — DLL3 expression screening (SHP77 vs A549) and target-dependent killing, immune-cell-dependent
- Efficacy — dose-response tumor-cell viability and caspase-3 apoptosis curves, the key functional readout for candidate selection
- Immune-response profiling — cytokine release (IFN-γ, TNF-α, IL-10), T-cell activation (CD4/CD8, CD69), and cytotoxic effectors (granzyme A/B, granulysin)
- CRS hazard — cytokine release in healthy-donor PBMCs, benchmarked against clinical positive controls (OKT3, blinatumomab, TGN1412) across time
- Single-cell resolution — a Xenium STAMP view that pinpoints the cellular source of each cytokine, adding mechanism to the functional result
Our team can adapt the tumor cell lines, immune-cell populations, and reference standards to fit your target, indication, and development goals.