To enhance the infiltration of adoptively transferred NK cells into pancreatic cancer (PC), Lee and Kang et al. developed the “NRP-body” – a fusion protein consisting of a mesothelin-targeting domain and the chemokine CXCL16 flanked by a furin cleavage site. In vitro and in vivo studies confirmed the release of CXCL16 from the NRP-body within the tumor tissue and the recruitment of transferred NK cells via the ERK-RhoA signaling cascade. In murine primary orthotopic and metastatic PC models treatment with NRP-body followed by NK cell therapy increased NK cell infiltration, reduced tumor burden, and increased overall survival.

Natural killer (NK) cells are primary immune cells that target cancer cells and can be used as a therapeutic agent against pancreatic cancer (PC). Despite their usefulness, NK-cell therapy is limited by tumor cell inhibition of NK-cell homing to tumor sites, thereby preventing a sustained antitumor immune response. One approach to successful cancer immunotherapy is to increase trafficking of NK cells to tumor tissues. Here, we developed an antibody-based NK cell-homing protein, named NK cell-recruiting protein-conjugated antibody (NRP-body). This consisted of The effect of this protein on infiltration of NK cells into primary and metastatic PC was evaluated in vitro and in murine pancreatic ductal adenocarcinoma PDAC models. The NRP-body increased NK-cell infiltration of tumors along a CXCL16 gradient (CXCL16 is cleaved from the NRP-body by furin expressed on the surface of PC cells). CXCL16 induced NK-cell infiltration by activating RhoA via the ERK signaling cascade. Administration of the NRP-body to PC model mice increased tumor tissue infiltration of transferred NK cells and reduced the tumor burden compared with that in controls. Overall survival (OS) of NRP-body-treated mice (even the metastasis models) was higher than that of mice receiving NK cells alone. In conclusion, increasing NK-cell infiltration into tumor tissues improved response to this cancer immunotherapy. The combination of an NRP-body with NK-cell therapy might be useful for treating PC.

Author Info: (1) Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology. (2) Immunology, College of Medicine, Konkuk University. (3) Aging Research Institute, Korea

Author Info: (1) Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology. (2) Immunology, College of Medicine, Konkuk University. (3) Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology. (4) Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology. (5) Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology. (6) Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology. (7) National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB). (8) National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology. (9) Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology. (10) Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine. (11) Korea Research Institute of Bioscience and Biotechnology. (12) Bioscience and Biotechnology, Chungnam National University. (13) Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology. (14) Aging research center, Korea Research Institute of Bioscience and Biotechnology kims@kribb.re.kr.