Browsing by Author "Huang, Yi-Chun"

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Canine CD8 T cells showing NK cytotoxic activity express mRNAs for NK cell-associated surface molecules
(2010-02-15)
Lin, Yi-Chun
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Huang, Yi-Chun
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Wang, Yu-Shan
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Juang, Rong-Huay
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Liao, Kuang-Wen
Natural killer (NK) cells have been considered to be a group of lymphocytes lacking clonally distributed receptors for antigens typical of T cells and B cells. in some mammalian species, including humans, a subpopulation of CD8(+) peripheral blood lymphocytes (PBLs) exhibits NK activity. This NK subpopulation has not been well characterized in mammals and its characterization is particularly poor in the dog. In this study, we demonstrated that a subset of canine CD8(+) cells derived from PBLs and lymphokine (IL-2)-activated killers (LAKs) of PBLs that was CD3(+), CD4(-), CD21(-), CD5(lo), alpha/beta TCR(+), and gamma/delta TCR(-) contained substantially higher levels of mRNAs for NK cell-related receptors (NKp30, NKp44, NKG2D, 2B4, and CD16 for PBL, and NKG2D and CD56 for LAK) than the corresponding CD8(-) cells. This subset of CD8(+) lymphocytes derived from LAKs also displayed significantly higher NK cytotoxic activity than the corresponding CD8(+) cells. In contrast, CD8(+) cells derived from nonstimulated PBLs showed very low levels of NK cytotoxic activity. Our results indicate that, in IL-2-stimulated PBLs, canine CD8(+) cells are an important subset associated with NK cytotoxic activity. (C) 2009 Elsevier B.V. All rights reserved.
Pharmacologically upregulated carcinoembryonic antigen-expression enhances the cytolytic activity of genetically-modified chimeric antigen receptor NK-92MI against colorectal cancer cells
(2018-08-03)
Shiozawa, Masayuki
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Chang, Chuan-Hsin
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Huang, Yi-Chun
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Chen, Yi-Ching
;
Chi, Mau-Shin
Background: The natural killer cell line, NK-92MI, is cytotoxic against various types of cancer. The aim of this study was to develop chimeric antigen receptor-modified (CAR) NK-92MI cells targeting carcinoembryonic antigen-expressing (CEA) tumours and increase killing efficacy by pharmacologically modifying CEA-expression. Result: We generated anti-CEA-CAR NK-92MI cells by retroviral vector transduction. This genetically-modified cell line recognised and lysed high CEA-expressing tumour cell lines (LS174T) at 47.54 +/- 12.60% and moderate CEA-expressing tumour cell lines (WiDr) at 31.14 +/- 16.92% at a 5:1 effector: target (E/T) ratio. The cell line did not lyse low CEA-expressing tumour cells (HCT116) as they did their parental cells (NK-92MI cells). The histone deacetylase-inhibitor (HDAC) sodium butyrate (NaB) and the methylation-inhibitor 5-azacytidine (5-AZA), as epigenetic modifiers, induced CEA-expression in HCT116 and WiDr cells. Although the IC50 of 5 fluorouracil (5-FU) increased, both cell lines showed collateral sensitivity to anti-CEA-CAR NK-92MI cells. The cytolytic function of anti-CEA-CAR NK-92MI cells was increased from 22.99 +/- 2.04% of lysis background to 69.20 +/- 11.92% after NaB treatment, and 69.70 +/- 9.93% after 5-AZA treatment, at a 10:1 UT ratio in HCT116 cells. The WiDr cells showed similar trend, from 22.99 +/- 4.01% of lysis background to 70.69 +/- 10.19% after NaB treatment, and 59.44 +/- 10.92% after 5-AZA treatment, at a 10:1 E/T ratio. Conclusions: This data indicates that the effector-ability of anti-CEA-CAR NK-92MI increased in a CEA-dependent manner. The combination of epigenetic-modifiers like HDAC-inhibitors, methylation-inhibitors, and adoptive-transfer of ex vivo-expanded allogeneic-NK cells may be clinically applicable to patients with in 5-FU resistant condition.