iCasp9 suicide-gene allodepleted donor T cells (CASPALLO)

Current understanding

Allodepleted donor T cells transduced with an inducible caspase-9 (iCasp9) suicide gene can be conditionally eliminated in vivo by the small-molecule dimerizer AP1903, offering a pharmacologic ‘off-switch’ for GvHD. This is intended to permit higher add-back T-cell doses after allo-HSCT to accelerate immune reconstitution while preserving the ability to abort GvHD if it emerges — an execution-layer graft-engineering strategy that does not alter who is referred to transplant but expands the safety envelope of T-cell add-back in T-depleted transplants. Evidence is early-phase trial (CASPALLO).

Evidence log

• 2026-07-01 — CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene: cross-connection with tcell-depleted-graft-ric: Both are graft-engineering execution-layer strategies for GvHD control; iCasp9 add-back could be layered onto T-cell-depleted RIC platforms to restore immune reconstitution without losing GvHD safety. (novelty: 4)

Open questions

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