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

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. What is already known on this topic Antigen-presenting scaffolds (Ag-scaffolds) represents a novel artificial antigen presenting cell (aAPC) technology designed to specifically expand tumor-specific T cells from peripheral blood mononuclear cells (PBMCs). Although Ag-scaffold technology has shown promising results in preclinical studies, its application in a large-scale clinical setting remains unexplored. What this study adds This study demonstrates the clinical applicability of the Ag-scaffold technology in patients with metastatic melanoma. The resulting multiple antigen-specific endogenously derived T cell (MASE-T) infusion product can be safely administered with no MASE-T related adverse events observed. How this study might affect research, practice or policy This study demonstrates the potential of the Ag-scaffold technology to expand low-frequent CD8+ tumor-specific T cell populations directly from peripheral blood. This proof of concept suggest that the Ag-scaffold technology could serve as a future alternative to treatment with tumor infiltrating lymphocytes (TILs) for patients not eligible for TIL therapy.