Redirecting NK cells to the lymph nodes to augment their lymphoma-targeting capacity
Laura Sanz-Ortega, Caroline Leijonhufvud, Lisanne Schoutens, Mélanie Lambert, Emily R. Levy, Agneta Andersson, Björn E. Wahlin, Mattias Carlsten
Abstract
CAR-NK cells can induce remission in lymphoma patients. We speculate that the full potential of adoptive NK cell immunotherapy against lymphoma is restricted by their poor lymph node (LN) homing capacity. Here, we have utilized a clinically approved transfection method with the aim of redirecting NK cells to LNs. Electroporation of ex vivo expanded NK cells with mRNAs coding for CCR7, CXCR5, and CD62L resulted in increased in vitro migration towards chemokines and mouse LN-derived supernatant. Following infusion into SCID/Beige mice, modified NK cells showed enhanced LN homing. Importantly, lymphoma patient-derived NK cells were equally well expanded and engineered as healthy donor NK cells, highlighting their translational potential. Additionally, the introduction of high-affinity CD16, together with the homing molecules, also augmented their ADCC capacity against autologous lymphoma cells. Hence, genetic engineering can be utilized to enhance NK cell LN homing. The homing concept may synergize with CAR- or monoclonal/bi-/tri-specific antibody-based approaches.