In this phase I trial, autologous tumor-associated antigen cytotoxic T cells (TAA-Ts) were induced ex vivo with three target antigens (WT-1, PRAME, or survivin). Treatment of patients with relapsed/refractory solid tumors expressing one of the three antigens was well tolerated, with no dose-limiting toxicities. Of 15 evaluable patients, 11 responded (stable disease or better at 45 days post-infusion). The highest dose showed the best clinical outcomes and trended toward improved PFS at 6 months. Products that induced responses had more CD8+ than CD4+ T cells. Most responders showed reduced circulating TAA DNA and evidence of antigen spreading.

PURPOSE: Tumor-associated antigen cytotoxic T cells (TAA-Ts) represent a new, potentially effective and nontoxic therapeutic approach for patients with relapsed or refractory solid tumors. In this first-in-human trial, we investigated the safety of administering TAA-Ts that target Wilms tumor gene 1, preferentially expressed antigen of melanoma, and survivin to patients with relapsed/refractory solid tumors. MATERIALS AND METHODS: TAA-T products were generated from autologous peripheral blood and infused over three dose levels: 1, 2, and 4 x 10(7) cells/m(2). Patients were eligible for up to eight infusions administered 4 to 7 weeks apart. We assessed dose limiting toxicity during the first 45 days after infusion. Disease response was determined within the context of a phase I trial. RESULTS: There were no dose-limiting toxicities. Of 15 evaluable patients, 11 (73%) with stable disease or better at day 45 postinfusion were defined as responders. Six responders remain without progression at a median of 13.9 months (range, 4.1 to 19.9 months) after initial TAA-Ts. Patients who were treated at the highest dose level showed the best clinical outcomes, with a 6-month progression-free survival of 73% after TAA-T infusion compared with a 38% 6-month progression-free survival with prior therapy. Antigen spreading and a reduction in circulating tumor-associated antigens using digital droplet polymerase chain reaction was observed in patients after TAA-T infusion. CONCLUSION: TAA-Ts safely induced disease stabilization, prolonged time to progression, and were associated with antigen spreading and a reduction in circulating tumor-associated antigen DNA levels in patients with relapsed/refractory solid tumors without lymphodepleting chemotherapy before infusion. TAA-Ts are a promising new treatment approach for patients with solid tumors.

Author Info: (1) 1Children's National Health System, Washington, DC. (2) 1Children's National Health System, Washington, DC. (3) 1Children's National Health System, Washington, DC. (4) 1Childre

Author Info: (1) 1Children's National Health System, Washington, DC. (2) 1Children's National Health System, Washington, DC. (3) 1Children's National Health System, Washington, DC. (4) 1Children's National Health System, Washington, DC. (5) 1Children's National Health System, Washington, DC. (6) 1Children's National Health System, Washington, DC. (7) 1Children's National Health System, Washington, DC. (8) 1Children's National Health System, Washington, DC. (9) 1Children's National Health System, Washington, DC. (10) 1Children's National Health System, Washington, DC. (11) 2National Institute of Allergy and Infectious Diseases, Bethesda, MD. (12) 1Children's National Health System, Washington, DC. (13) 1Children's National Health System, Washington, DC. (14) 1Children's National Health System, Washington, DC. (15) 1Children's National Health System, Washington, DC. (16) 1Children's National Health System, Washington, DC. (17) 1Children's National Health System, Washington, DC. (18) 1Children's National Health System, Washington, DC. (19) 1Children's National Health System, Washington, DC. (20) 1Children's National Health System, Washington, DC.