Lymphodepletion

Lymphodepletion refers to the intentional reduction of circulating and resident lymphocytes, a process most commonly employed as a preconditioning step for adoptive cell therapies such as Chimeric Antigen Receptor (CAR) T-cell therapy or tumor-infiltrating lymphocytes (TILs) (StatPearls, 2023). This physiological state is typically induced using chemotherapy agents—most notably the combination of cyclophosphamide and fludarabine—or total body irradiation (PubMed, PMID: 21257471). The primary biological objective is to eliminate endogenous T cells that compete for essential homeostatic cytokines like IL-7 and IL-15, which are often referred to as 'cytokine sinks' (Nature Reviews Clinical Oncology, 2020). By clearing these sinks, lymphodepletion provides a favorable environment that promotes the rapid expansion, activation, and long-term persistence of the infused therapeutic cells (NIH, 2021). Additionally, it helps suppress host regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) that might otherwise inhibit the anti-tumor immune response. Clinically, while lymphodepletion is essential for the efficacy of many cell-based immunotherapies, it carries significant risks including severe bone marrow suppression and an increased vulnerability to life-threatening infections (Journal of Clinical Oncology, 2018).

Other names

LymphoablationLymphocytic depletionPreconditioning regimenNon-myeloablative conditioning

Lymphodepletion is a systemic process induced by cytotoxic agents or radiation that eliminates endogenous lymphocytes to reduce competition for homeostatic cytokines (IL-7 and IL-15), thereby facilitating the expansion and persistence of infused adoptive cell therapies like CAR-T cells.