Lymphodepletion and cellular immunotherapy

Many adoptive cellular therapies (ACT) for cancer have advanced to the clinic for testing and treatment, including chimeric antigen receptor T-cell (CAR T-cell) therapy, tumor-infiltrating lymphocyte (TIL) therapy, and ex vivo expanded lymphokine-activated natural killer cells. Conditioning patients with lymphodepleting chemotherapy was a pivotal advance in enabling these therapies. In this review, we will discuss the various regimens that have been used and their associated toxicities. Only a limited number of studies have directly compared two or more regimens. Intermediate dose cyclophosphamide and fludarabine-based regimens are emerging as a popular approach that balances efficacy and safety. We will also discuss methods of avoiding lymphodepletion that are being developed to decrease toxicity of cellular immunotherapies.