Safety and feasibility of serial autologous mTAA T cell infusions in pancreatic cancer
Musher BL, Vasileiou S, Smaglo BG, et al. Autologous Multiantigen-Targeted T Cell Therapy for Pancreatic Cancer: A Phase 1/2 Trial. Nature Medicine. 2026; (doi: 10.1038/s41591-025-04043-5).
Researchers are encouraged by the early performance of multi-antigen T-cells in the setting of pancreatic ductal adenocarcinoma (PDAC), a cancer that has largely resisted immunotherapy. Heterogeneous expression of tumor-associated antigens (TAAs), which facilitates immune evasion, helps to undermine the treatment in PDAC, but scientists believe targeting several antigens at once may offer an effective work-around. They launched the Phase I/II TACTOPS trial to evaluate autologous T-cells specific to five carefully selected TAAs. Manufacturing and infusion were feasible, successful, and well tolerated by study participants at all disease levels: stable and/or responsive to chemotherapy (Arm A), refractory to chemotherapy (Arm B), and potentially resectable (Arm C). A total of 37 patients with advanced PDAC received 140 infusions of multi-antigen T cells (mTAA), with no resulting autoimmunity, cytokine release syndrome, or neurotoxicity. Outcomes in Arm A — including an 84.6% disease control rate, median 7.5-month duration of response, and median overall survival of 14.1 months — were particularly impressive, study authors report, considering patients had already received 3-4 months of chemotheraworkaroundpy before their first T-cell infusion. Future research, they suggest, should explore TAA T cells as a single therapeutic modality or in combination with other novel immunotherapies or routine chemotherapy.