Exercise-Mobilized Donor Lymphocytes Enhance Blinatumomab Activity Against B-ALL.

Background: Donor lymphocyte infusion (DLI) is used to prevent and treat leukemic relapse after allogeneic hematopoietic cell transplantation, although its efficacy against lymphoid malignancies remains limited. Blinatumomab (Blina), a CD3/CD19 bispecific T-cell engager, is increasingly used to enhance DLI activity against acute lymphoblastic leukemia (ALL). We previously demonstrated that exercise-mobilized DLI (DLI-X) exhibits superior anti-leukemic activity against myeloid malignancies. Here, we investigated whether DLI-X combined with Blina enhances cytotoxicity against CD19 Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy participants at rest (DLI) and during the final stage of a 20-minute graded cycling protocol to 80% VO Results: DLI and DLI-X alone exhibited limited cytotoxicity against RS4;11 cells. Blina significantly enhanced cytotoxicity of both products, with DLI-X+Blina demonstrating >20% greater tumor killing than DLI+Blina (~85% vs. ~62%). Compared with DLI, DLI-X displayed enhanced Blina-induced T-cell effector function, including increased CD107a degranulation, greater TNF-α production by CD4 Conclusions: Exercise mobilizes T cells with enhanced responsiveness to Blina, resulting in superior activation and cytotoxicity against CD19 Trial registration: ClinicalTrials.gov, NCT06643221. Registered retrospectively on October 8, 2024.