Less is more: Low-strength type I interferon signaling enhances CAR T cell therapy

Current CAR T cell therapies produce durable remissions in B cell malignancies, yet primary resistance and relapse remain major challenges.1,2 Most efforts to improve efficacy have focused on the receptor or the genome encoding it, through new receptor and costimulatory designs, additional genetic modifications, rewiring of intracellular signaling, phenotype-directed differentiation, or combination regimens.3 These strategies are powerful, but most introduce a new genetic element or a novel biologic agent and with it, a new engineering, manufacturing, and regulatory burden.