Trispecific antibodies
Antibodies engineered to bind three things at once, for example a tumour antigen, a T-cell activator and a co-stimulatory signal, to make a stronger or more selective immune attack.
Overview
Trispecific antibodies extend the bispecific T-cell engager concept with a third binding arm: a co-stimulatory receptor such as CD28 to strengthen T-cell activation, a second tumour antigen to prevent escape, or a half-life-extending domain. Early trials in myeloma, lymphoma and solid tumours are under way, and the format is also used in NK cell engagers. Complexity in manufacturing and the risk of excessive activation are the main challenges.
How it works
Three binding domains are assembled on one engineered antibody scaffold so that binding to the tumour cell clusters two immune signals on the same effector cell.
- Co-stimulation may deepen and prolong responses
- Dual tumour antigens reduce antigen escape
- Early stage
- Manufacturing complexity
- Potential for over-activation and toxicity
Latest papers
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