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Title 

An antibody designed to improve adoptive NK-cell therapy inhibits pancreatic cancer progression in a murine model

Authors 

Jaemin LeeT H KangWonbeak YooHyunji ChoiSungyea JoKyungsu KongSang-Rae LeeSun-Uk KimJi-Su KimD ChoJanghwan KimJ Y KimEun Soo KwonSeokho Kim

Publisher 

American Association for Cancer Research

Issue Date 

2019

Citation 

Cancer Immunology Research

Abstract 

Natural killer (NK) cells are primary immune cells that target cancer cells and can be used as a therapeutic agent against pancreatic cancer. Despite the usefulness of NK cells, 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). The effect of NRP-body on infiltration of NK cells into primary and metastatic pancreatic cancer was evaluated in vitro and in murine pancreatic ductal adenocarcinoma 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 pancreatic cancer cells). CXCL16 induced NK-cell infiltration by activating RhoA via the ERK signaling cascade. Administration of the NRP-body to pancreatic cancer model mice increased tumor tissue infiltration of transferred NK cells and reduced the tumor burden compared with that in controls. Overall survival 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 pancreatic cancer.

URI 

https://doi.org/10.1158/2326-6066.CIR-18-0317

ISSN 

2326-6066

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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