T-cell engaging bispecific antibodies (T-cell engagers)
A T-cell engager is a bispecific antibody that binds a tumor-surface antigen on one arm and CD3 on T cells on the other, bringing T cells to the tumor cell. Examples are mosunetuzumab (CD20) and tarlatamab (DLL3).
Definition
A T-cell engaging bispecific antibody (T-cell engager) has two binding arms: one binds an antigen on the tumor cell and the other binds CD3 on T cells. By bringing the two together, it activates T cells against the tumor cell without the need for the T cell's own antigen specificity.
Examples
- Mosunetuzumab: CD20 × CD3, for B-cell lymphoma.
- Tarlatamab: DLL3 × CD3, for small cell lung cancer.
Dosing issues
Strong T-cell activation can cause cytokine release syndrome, most often after the first dose, so these drugs are usually given with step-up dosing. Their dosing intervals are also chosen with trough and peak exposure in mind.
On this site
The tarlatamab regimen analysis asks whether matching the average exposure alone can set the dosing interval, the summary-value analysis asks what published PK summaries determine, the mosunetuzumab reimplementation examines step-up dosing, and the decision framework organizes public evidence for the next experiment.
Frequently asked questions
How does a T-cell engager differ from CAR-T therapy?
A T-cell engager is an off-the-shelf antibody that redirects the patient’s own T cells; CAR-T therapy uses T cells that are collected, engineered and given back.
Why are T-cell engagers started at low doses?
To lower the first concentration peak and the risk of cytokine release syndrome, then increase to the target dose (step-up dosing).