Dang-Huan Pham1, Ju-Sun Kim2, Sang-Ki Kim2, Dong-Jun Shin2,3, Nguyen-Thanh-Tung Uong3, Hoon Hyun1, Mee Sun Yoon4, Sin Jae Kang5, Young Jae Ryu5, Jin Seong Cho5, Jung Han Yoon5, Ji Shin Lee6, Duck Cho7, Soo-Hyeon Lee8, Min Ho Park9. 1. Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea. 2. Department of Companion & Laboratory Animal Science, Kongju National University, Yesan, Republic of Korea. 3. Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea. 4. Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, Republic of Korea. 5. Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea. 6. Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea. 7. Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 8. Department of Integrated Life Science and Technology, Kongju National University, Yesan, Republic of Korea. 9. Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea mhpark@chonnam.ac.kr.
Abstract
BACKGROUND/AIM: The inhibition of a disintegrin and metalloproteinase (ADAM) has the potential to become a novel approach for natural killer (NK) cell-based cancer immunotherapy. Thus, the aim of this study was to investigate the influence of ADAM10 and ADAM17 inhibitors on expanded NK cell to enhance antibody-dependent cellular cytotoxicity (ADCC) in breast cancer cell lines. MATERIALS AND METHODS: NK cells were expanded in medium supplemented with an ADAM10 or ADAM17 inhibitor to prevent the shedding of soluble CD16/FcγRIII. The expression level of CD16 and production of interferon-gamma (IFN-γ) was detected by flow cytometry using specific antibodies. ADCC activity of expanded NK cells was estimated in trastuzumab treated breast cancer cell lines such as MCF-7, MDA-MB-231, SKBR3, and BT-474 cells. RESULTS: The ADAM17 inhibitor increased the purity of expanded NK cells to 90% after 14 days at 5 and 10 μM in vitro (p=0.043). However, the expansion rate of NK cells was decreased at 10 μM of the ADAM 17 inhibitor (p=0.043). Inhibition of ADAM10 suppressed the expansion of NK cells, although the NK purity was increased at 1 μM of the inhibitor. The expression of CD16 was significantly increased at 1 and 5 μM of the ADAM17 inhibitor (p=0.046, 0.028, respectively) during the culturing period. Inhibition of ADAM10 reduced the expression of CD16 on NK cells. The cytotoxic activity of the ADAM17 inhibitor treated NK cells against MCF-7 (p=0.039) and BT-474 (p=0.027) cells was significantly elevated. The ADCC activity of NK cells treated with 5 μM of ADAM17 inhibitor was significantly increased against SKBR-3 and BT-474 (p=0.027). Inhibition of ADAM17 increased the production of IFN-γ in expanded NK cells. CONCLUSION: The inhibition of ADAM17 enhanced the purity of expanded NK cells and the ADCC activity of these cells against trastuzumab treated breast cancer cell lines. Copyright
BACKGROUND/AIM: The inhibition of a disintegrin and metalloproteinase (ADAM) has the potential to become a novel approach for natural killer (NK) cell-based cancer immunotherapy. Thus, the aim of this study was to investigate the influence of ADAM10 and ADAM17 inhibitors on expanded NK cell to enhance antibody-dependent cellular cytotoxicity (ADCC) in breast cancer cell lines. MATERIALS AND METHODS: NK cells were expanded in medium supplemented with an ADAM10 or ADAM17 inhibitor to prevent the shedding of soluble CD16/FcγRIII. The expression level of CD16 and production of interferon-gamma (IFN-γ) was detected by flow cytometry using specific antibodies. ADCC activity of expanded NK cells was estimated in trastuzumab treated breast cancer cell lines such as MCF-7, MDA-MB-231, SKBR3, and BT-474 cells. RESULTS: The ADAM17 inhibitor increased the purity of expanded NK cells to 90% after 14 days at 5 and 10 μM in vitro (p=0.043). However, the expansion rate of NK cells was decreased at 10 μM of the ADAM 17 inhibitor (p=0.043). Inhibition of ADAM10 suppressed the expansion of NK cells, although the NK purity was increased at 1 μM of the inhibitor. The expression of CD16 was significantly increased at 1 and 5 μM of the ADAM17 inhibitor (p=0.046, 0.028, respectively) during the culturing period. Inhibition of ADAM10 reduced the expression of CD16 on NK cells. The cytotoxic activity of the ADAM17 inhibitor treated NK cells against MCF-7 (p=0.039) and BT-474 (p=0.027) cells was significantly elevated. The ADCC activity of NK cells treated with 5 μM of ADAM17 inhibitor was significantly increased against SKBR-3 and BT-474 (p=0.027). Inhibition of ADAM17 increased the production of IFN-γ in expanded NK cells. CONCLUSION: The inhibition of ADAM17 enhanced the purity of expanded NK cells and the ADCC activity of these cells against trastuzumab treated breast cancer cell lines. Copyright
Authors: Carlos E Sanchez; Ehsan P Dowlati; Ashley E Geiger; Kajal Chaudhry; Matthew A Tovar; Catherine M Bollard; Conrad Russell Y Cruz Journal: Transplant Cell Ther Date: 2020-09-29
Authors: Ying Gong; Roel G J Klein Wolterink; Valeriia Gulaia; Silvie Cloosen; Femke A I Ehlers; Lotte Wieten; Yvo F Graus; Gerard M J Bos; Wilfred T V Germeraad Journal: Cancers (Basel) Date: 2021-05-25 Impact factor: 6.639