Programmable Immunity

This week on Reprogrammed, Jack and Annie tackle a key limitation in CAR T cell therapy for solid tumors: poor trafficking to the tumor site. Centered on the 2010 study by Craddock et al., this episode explores how engineering T cells to express the chemokine receptor CCR2b—matching the tumor’s secretion of CCL2—can dramatically improve tumor infiltration without sacrificing cytotoxic function. Through in vitro migration assays and in vivo imaging in mouse models, the team unpacks how this strategy adds a modular “navigation” system to CAR T cells, allowing them to home in on their targets more effectively.With references to past episodes on co-stimulatory signaling, persistence, and dual-antigen targeting, this episode expands the design philosophy of CAR T therapy from “stronger” to “smarter.” Annie and Jack also look ahead to next week’s discussion of split-signal CARs that promise greater safety through precision control—bringing us closer to truly programmable immunity.