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      저자 : Kong Kyungsu (검색결과 1 건)
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      • An Antibody Designed to Improve Adoptive NK-Cell Therapy Inhibits Pancreatic Cancer Progression in a Murine Model

        Lee, Jaemin,Kang, Tae Heung,Yoo, Wonbeak,Choi, Hyunji,Jo, Seongyea,Kong, Kyungsu,Lee, Sang-Rae,Kim, Sun-Uk,Kim, Ji-Su,Cho, Duck,Kim, Janghwan,Kim, Jeong-Yoon,Kwon, Eun-Soo,Kim, Seokho AMERICAN ASSOCIATION FOR CANCER RESEARCH 2019 CANCER IMMUNOLOGY RESEARCH Vol.7 No.2

        <P>The homing of natural killer (NK) cells is often inhibited by pancreatic cancer tumors. A mesothelin-directed antibody conjugated to a cleavable NK cell—recruiting chemokine increased NK-cell infiltration of PDAC tumors, reduced tumor burden, and improved survival.</P><P>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 <I>in vitro</I> 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.</P>

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