Phase 1 FH-WT1-E50 WT1-targeted TCR‑T plus azacitidine for MRD+ AML

This Phase 1 study at Fred Hutchinson Cancer Center evaluates FH‑WT1‑E50, an autologous CD4+/CD8+ T-cell product genetically transduced to express an HLA‑A02:01–restricted, WT1-specific T-cell receptor (TCR‑T; MOA: MHC-presented WT1 peptide recognition leading to T-cell cytotoxic killing of WT1-expressing leukemia cells), given with azacitidine (DNA hypomethylating agent that inhibits DNA methyltransferases and promotes epigenetic reprogramming). Patients first undergo leukapheresis, then receive azacitidine, followed by azacitidine plus FH‑WT1‑E50 infusion; if enough cells are available, a second azacitidine + TCR‑T infusion can occur as early as day 28 and up to 1 year. The target population is minimal residual disease (MRD)–positive AML with WT1 expression and HLA‑A02:01 positivity (HLA‑A*02:01 is common in many populations, roughly ~40–50%, making the approach broadly applicable but still HLA-gated). The key angle is moving engineered TCR‑T into the MRD setting, where tumor burden is lower and immune therapies may have a better chance to deepen remission; today’s care for MRD+ AML commonly involves additional consolidation strategies such as hypomethylating agents (including azacitidine), venetoclax-based therapy in some contexts, and/or consideration of allogeneic stem cell transplant depending on risk, fitness, and prior therapy.