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Cancer Immunology Research

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An Antibody Designed to Improve Adoptive NK-Cell Therapy Inhibits Pancreatic Cancer Progression in a Murine Model

Jaemin Lee, Tae Heung Kang, Wonbeak Yoo, Hyunji Choi, Seongyea Jo, Kyungsu Kong, Sang-Rae Lee, Sun-Uk Kim, Ji-Su Kim, Duck Cho, Janghwan Kim, Jeong-Yoon Kim, Eun-Soo Kwon and Seokho Kim
Jaemin Lee
Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, South Korea.
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Tae Heung Kang
Department of Immunology, School of Medicine, Konkuk University, Seoul, South Korea.
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Wonbeak Yoo
Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
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Hyunji Choi
Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
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Seongyea Jo
Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
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Kyungsu Kong
Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, South Korea.
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Sang-Rae Lee
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, South Korea.
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Sun-Uk Kim
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, South Korea.
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  • ORCID record for Sun-Uk Kim
Ji-Su Kim
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, South Korea.
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  • ORCID record for Ji-Su Kim
Duck Cho
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea.
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Janghwan Kim
Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
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  • ORCID record for Janghwan Kim
Jeong-Yoon Kim
Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, South Korea.
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  • ORCID record for Jeong-Yoon Kim
Eun-Soo Kwon
Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
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  • For correspondence: kims@kribb.re.kr eunsoo.kwon@kribb.re.kr
Seokho Kim
Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
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  • For correspondence: kims@kribb.re.kr eunsoo.kwon@kribb.re.kr
DOI: 10.1158/2326-6066.CIR-18-0317 Published February 2019
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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.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • J. Lee and T.H. Kang share first authorship of this article.

  • E.-S. Kwon and S. Kim share senior authorship of this article.

  • Received May 11, 2018.
  • Revision received September 12, 2018.
  • Accepted November 28, 2018.
  • Published first December 4, 2018.
  • ©2018 American Association for Cancer Research.
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Cancer Immunology Research: 7 (2)
February 2019
Volume 7, Issue 2
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An Antibody Designed to Improve Adoptive NK-Cell Therapy Inhibits Pancreatic Cancer Progression in a Murine Model
Jaemin Lee, Tae Heung Kang, Wonbeak Yoo, Hyunji Choi, Seongyea Jo, Kyungsu Kong, Sang-Rae Lee, Sun-Uk Kim, Ji-Su Kim, Duck Cho, Janghwan Kim, Jeong-Yoon Kim, Eun-Soo Kwon and Seokho Kim
Cancer Immunol Res February 1 2019 (7) (2) 219-229; DOI: 10.1158/2326-6066.CIR-18-0317

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An Antibody Designed to Improve Adoptive NK-Cell Therapy Inhibits Pancreatic Cancer Progression in a Murine Model
Jaemin Lee, Tae Heung Kang, Wonbeak Yoo, Hyunji Choi, Seongyea Jo, Kyungsu Kong, Sang-Rae Lee, Sun-Uk Kim, Ji-Su Kim, Duck Cho, Janghwan Kim, Jeong-Yoon Kim, Eun-Soo Kwon and Seokho Kim
Cancer Immunol Res February 1 2019 (7) (2) 219-229; DOI: 10.1158/2326-6066.CIR-18-0317
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