Single-center phase 1-2 trial of autologous multiantigen-targeted T cell therapy for advanced pancreatic ductal adenocarcinoma

T cell therapy has proven challenging for pancreatic ductal adenocarcinoma (PDAC), partly due to heterogeneous expression of tumor-associated antigens (TAAs). A phase 1-2 trial at Baylor College of Medicine (Houston, TX) evaluated an ex vivo expanded, polyclonal, T helper 1 cell-polarized T cell product targeting five TAAs (PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1) for PDAC. This autologous T cell product was administered (1 x 10⁷ cells/m² per infusion) monthly to patients with advanced PDAC responding (arm A; n=13) or refractory (arm B; n=12) to first-line chemotherapy, or with resectable disease (arm C, n=12). Primary endpoints were safety and feasibility of completing six infusions. Of 56 patients procured 37 were infused, with only one treatment-related serious adverse event. Disease control rate was 84.6% (95% CI 54.6-98.1) in arm A and 25% (5.5-57.2) in arm B, whereas in arm C two of nine resected patients remained disease free after 66 months of follow-up. The infused cells persisted up to 12 months posttreatment, and elevated levels of tumor-directed T cells were detected during dosing and follow-up in responders. The authors conclude that further investigation of this approach, either as a single agent or combined with other modalities, is warranted.