TY - JOUR T1 - An antibody designed to improve adoptive NK-cell therapy inhibits pancreatic cancer progression in a murine model JF - Cancer Immunology Research JO - Cancer Immunol Res DO - 10.1158/2326-6066.CIR-18-0317 SP - canimm.0317.2018 AU - Lee, Jaemin AU - Kang, Tae Heung AU - Yoo, Wonbeak AU - Choi, Hyunji AU - Jo, Seongyea AU - Kong, Kyungsu AU - Lee, Sang-Rae AU - Kim, Sun-Uk AU - Kim, Ji-Su AU - Cho, Duck AU - Kim, Janghwan AU - Kim, Jeong-Yoon AU - Kwon, Eun-Soo AU - Kim, Seokho Y1 - 2018/01/01 UR - http://cancerimmunolres.aacrjournals.org/content/early/2018/12/04/2326-6066.CIR-18-0317.abstract N2 - 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. ER -