Adoptive cell therapy using cultured tumor infiltrating lymphocytes for Japanese patients with refractory melanoma

Three patients who failed immune-checkpoint inhibitors were treated with the adoptive cell therapy using ex vivo cultured tumor infiltrating lymphocytes (TIL-ACT), which was composed of preparation of TIL culture, lympho-depleting non-myeloablative preconditioning, TIL infusion, and following relatively low dose intravenous IL-2 administration. Then we evaluated treatment feasibility, safety and clinical response. To further investigate the relationship between the tumor microenvironment and the patient's clinical course, we performed gene expression analysis of the pre-treatment tumor cells and immunohistochemistry of the tumor tissue focusing on delineating the immune components and immunologic milieu within the tumor. Together with the results of genomic and immunological analysis of ex vivo cultured TILs by flowcytometry and quantitative real-time polymerase chain reaction, we considered the various immunostimulating or immunosupprrsive factors giving influence on the effects of the conducted TIL-ACT. Gene expression in melanoma cells sorted from metastatic tumor tissue was measured. Three independent experiments were performed using different donors for each experiment.