Safety and feasibility of blood-derived Multiple Antigen-Specific Endogenous T cells (MASE-T) for metastatic melanoma

Publication date: Jul 02, 2025

Background: Tumor infiltrating lymphocyte (TIL) therapy is effective in metastatic melanoma, but the need for resectable tumor tissue limits its accessibility. Antigen-presenting scaffolds (Ag-scaffolds) are 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 co-attached interleukin 2 (IL-2), interleukin 21 (IL-21), and MHC I molecules loaded with the top 30 most frequently expressed TAAs in melanoma patients. The resulting multiple antigen-specific endogenously derived T cell (MASE-T) infusion product is characterized by increased 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 metastatic melanoma. Methods: In this phase I, first-in-human, clinical trial, six patients with ICI-resistant melanoma were treated with MASE-T cells preceded by three days of lymphodepleting chemotherapy with cyclophosphamide and fludarabine phosphate. 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 three out of six (50%) of patients having stable disease six weeks post treatment. Conclusions: This trial demonstrates that Ag-scaffold-driven expansion of TAA-specific T cells from the peripheral blood of patients with melanoma 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. Trial registration: Clinicaltrials.gov NCT04904185, registered 22.05.2021.

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