Directed bone marrow homing as a strategy to embed T cells (360G-Wellcome-201049_Z_16_Z)

T-cell therapies are quickly emerging as highly promising candidates for the treatment of infection, cancer and autoimmune disease. Critical for the success of these therapies is the need for T cells to engraft efficiently and then persist long-term. Current clinical protocols have employed ‘conditioning’ with chemo- or radiotherapy, with or without exogenous cytokines, to aid engraftment and survival of transferred cells. But these approaches are associated with significant risks to already sick patients and only have variable success in ensuring the persistence of adoptively transferred T cells. There is an important unmet medical need to develop safer and more effective ‘one-shot’ strategies to promote both the initial engraftment and survival of therapeutic T cells in patients. Professor Ronjon Chakraverty has identified a completely novel strategy to overcome these hurdles. It involves overexpressing using the chemokine receptor CXCR4 to direct the T cells to the bone marrow, where they receive specific niche signals that promote engraftment and survival. Across multiple clinical applications, this strategy is designed to achieve a lasting therapeutic effect with a single dose of T cells.