Safety and feasibility of blood-derived multiple antigen-specific endogenously derived T cells (MASE-T) for metastatic melanoma.

Background: Tumor-infiltrating lymphocyte (TIL) therapy is effective in metastatic melanoma (MM), but the need for resectable tumor tissue limits its accessibility. Antigen-presenting scaffolds (Ag-scaffolds) constitute a technology developed for the specific expansion of tumor-associated antigen (TAA)-specific T cells directly from peripheral blood. Ag-scaffolds are built on a dextran backbone with coattached interleukin 2 (IL-2), interleukin 21 (IL-21), and major histocompatibility complex class I molecules loaded with the top 30 most frequently expressed TAAs in MM patients. The resulting multiple antigen-specific endogenously derived T-cell (MASE-T) infusion product is enriched for CD8+ TAA-specific T cells. We hypothesize that treatment with MASE-T therapy is safe and feasible in patients with immune checkpoint inhibitor (ICI)-resistant MM. Patients and methods: In this phase I, first-in-human, clinical trial (NCT04904185), six patients with ICI-resistant MM received MASE-T therapy preceded by 3 days of lymphodepleting chemotherapy with cyclophosphamide and fludarabine phosphate. The primary endpoint was the safety and feasibility of the treatment. Results: MASE-T cells were successfully expanded in 88% (7/8) of the included patients, and most MASE-T products were enriched for T-cell populations targeting multiple TAAs. Administration of MASE-T therapy was safe with no MASE-T-related toxicities. Clinical efficacy was limited, with 3 out of 6 (50%) patients having stable disease 6 weeks after treatment. Conclusions: This trial demonstrates that Ag-scaffold-driven expansion of TAA-specific T cells from the peripheral blood of patients with MM is feasible, and the resulting MASE-T infusion product can be safely administered. However, further development is required to unleash the full potential of this technology.