Trastuzumab-Mediated Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Enhances Natural Killer Cell Cytotoxicity in HER2-Overexpressing Ovarian Cancer

被引:0
|
作者
Hong, Sa Deok [1 ]
Katuwal, Nar Bahadur [1 ]
Kang, Min Sil [1 ]
Ghosh, Mithun [1 ]
Park, Seong Min [1 ]
Kim, Tae Hoen [2 ]
Baek, Young Seok [1 ,3 ]
Lee, Seung Ryeol [4 ]
Moon, Yong Wha [5 ]
机构
[1] CHA Univ, Grad Sch, Dept Biomed Sci, Seongnam 13488, South Korea
[2] CHA Univ, CHA Bundang Med Ctr, Dept Pathol, Seongnam 13496, South Korea
[3] CHA Biotech, R&D Div, Immunotherapy Team, New Biol Ent NBE Res, Seongnam Si 13488, South Korea
[4] CHA Univ, CHA Bundang Med Ctr, Dept Urol, Seongnam Si 13496, South Korea
[5] CHA Univ, CHA Bundang Med Ctr, Dept Internal Med, Div Hematol Oncol, Seongnam Si 13496, South Korea
基金
新加坡国家研究基金会;
关键词
HER2-overexpressed ovarian cancer; trastuzumab; NK cell; ADCC; BREAST-CANCER; FC-RECEPTORS; THERAPY; MECHANISMS; RESISTANCE; HER2;
D O I
10.3390/ijms252111733
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ovarian cancer is the deadliest gynecologic cancer. Although human epidermal growth factor receptor-2 (HER2) overexpression, a poor prognostic molecular marker in ovarian cancer, is found in almost 30% of ovarian cancer cases, there are no established therapies for HER2-overexpressing ovarian cancer. In this study, we investigated the efficacy of combined samfenet, a biosimilar compound of trastuzumab, and natural killer (NK) cells in preclinical model of HER2-overexpressing ovarian cancer. Firstly, we screened the HER2 expression in three ovarian cancer cell lines and eight ovarian cancer patient-derived tumor xenograft (PDTX) samples. Then, immunohistochemistry and silver in situ hybridization (SISH) were performed following clinical criteria. HER2-overexpressing cells exhibited the highest sensitivity to samfenet compared with low-HER2-expressing cells. In addition, the combination of samfenet with natural killer (NK) cells resulted in significantly enhanced sensitivity to HER2-overexpressing cells and showed a significant antitumor effect on PDTX mice compared with monotherapy. It is known that anti-HER2-humanized IgG1 monoclonal antibodies, including trastuzumab, induce antibody-dependent cellular cytotoxicity (ADCC). Consequently, the combination of samfenet with NK cells demonstrated NK cell-mediated ADCC, as confirmed using an in vitro NK cytotoxicity assay and in vivo antitumor efficacy. A transferase dUTP nick end labeling (TUNEL) assay using xenografted tumors further supported the ADCC effects based on the increase in the number of apoptotic cells in the combination group. Furthermore, high HER2 expression was associated with shorter progression-free survival and overall survival based on public mRNA expression data. In this study, we demonstrated that the combination of samfenet and NK cell therapy could be a promising treatment strategy for patients with HER2-overexpressing ovarian cancer, through ADCC effects. Therefore, this study supports a rationale for further clinical studies of the combination of samfenet and NK cells as a therapy for patients with HER2-overexpressing ovarian cancer.
引用
收藏
页数:17
相关论文
共 50 条
  • [21] Anti-KL-6/MUC1 monoclonal antibody reverses resistance to trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity by capping MUC1
    Namba, Masashi
    Hattori, Noboru
    Hamada, Hironobu
    Yamaguchi, Kakuhiro
    Okamoto, Yohei
    Nakashima, Taku
    Masuda, Takeshi
    Sakamoto, Shinjiro
    Horimasu, Yasushi
    Miyamoto, Shintaro
    Iwamoto, Hiroshi
    Fujitaka, Kazunori
    Kohno, Nobuoki
    CANCER LETTERS, 2019, 442 : 31 - 39
  • [22] T-cell activation enhances anti-HER2-mediated antibody-dependent cellular cytotoxicity in gastric cancer
    Zirui Xue
    Zhaoming Wang
    Dan Liu
    Bosen Li
    Zhaodong Sun
    Junjie Zhao
    Haojie Li
    Xuefei Wang
    Yihong Sun
    Immunologic Research, 2025, 73 (1)
  • [23] EFFECT OF SHORT-TERM ETHANOL INTAKE ON ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY (ADCC) IN RATS
    SABOL, M
    PAULIKOVA, E
    PHYSIOLOGICAL RESEARCH, 1992, 41 (03) : 257 - 260
  • [24] E-cadherin expression on human carcinoma cell affects trastuzumab-mediated antibody-dependent cellular cytotoxicity through killer cell lectin-like receptor G1 on natural killer cells
    Yamauchi, Chisako
    Fujii, Satoshi
    Kimura, Taichi
    Kuwata, Takeshi
    Wada, Noriaki
    Mukai, Hirofumi
    Matsumoto, Naoki
    Fukayama, Masashi
    Ochiai, Atsushi
    INTERNATIONAL JOURNAL OF CANCER, 2011, 128 (09) : 2125 - 2137
  • [25] Inhibitory receptors for HLA class I as immune checkpoints for natural killer cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy
    Nicky A. Beelen
    Femke A. I. Ehlers
    Gerard M. J. Bos
    Lotte Wieten
    Cancer Immunology, Immunotherapy, 2023, 72 : 797 - 804
  • [26] Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicity
    Minh Ngoc Duong
    Aurore Cleret
    Eva-Laure Matera
    Kamel Chettab
    Doriane Mathé
    Sandrine Valsesia-Wittmann
    Béatrice Clémenceau
    Charles Dumontet
    Breast Cancer Research, 17
  • [27] A Neutralizing Antibody Assay Based on a Reporter of Antibody-Dependent Cell-Mediated Cytotoxicity
    Wu, Yuling
    Li, Jia J.
    Kim, Hyun Jun
    Liu, Xu
    Liu, Weiyi
    Akhgar, Ahmad
    Bowen, Michael A.
    Spitz, Susan
    Jiang, Xu-Rong
    Roskos, Lorin K.
    White, Wendy I.
    AAPS JOURNAL, 2015, 17 (06): : 1417 - 1426
  • [28] A Neutralizing Antibody Assay Based on a Reporter of Antibody-Dependent Cell-Mediated Cytotoxicity
    Yuling Wu
    Jia J. Li
    Hyun Jun Kim
    Xu Liu
    Weiyi Liu
    Ahmad Akhgar
    Michael A. Bowen
    Susan Spitz
    Xu-Rong Jiang
    Lorin K. Roskos
    Wendy I. White
    The AAPS Journal, 2015, 17 : 1417 - 1426
  • [29] Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicity
    Minh Ngoc Duong
    Cleret, Aurore
    Matera, Eva-Laure
    Chettab, Kamel
    Mathe, Doriane
    Valsesia-Wittmann, Sandrine
    Clemenceau, Beatrice
    Dumontet, Charles
    BREAST CANCER RESEARCH, 2015, 17
  • [30] Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells
    Friedman, Jay
    Padget, Michelle
    Lee, John
    Schlom, Jeffrey
    Hodge, James
    Allen, Clint
    ORAL ONCOLOGY, 2019, 90 : 38 - 44