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
  • [31] Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor immunotherapy with therapeutic antibodies
    Seidel, Ursula J. E.
    Schlegel, Patrick
    Lang, Peter
    FRONTIERS IN IMMUNOLOGY, 2013, 4
  • [32] The combination of trastuzumab and pertuzumab administered at approved doses may delay development of trastuzumab resistance by additively enhancing antibody-dependent cell-mediated cytotoxicity
    Toth, Gabor
    Szoor, Arpad
    Simon, Laszlo
    Yarden, Yosef
    Szollosi, Janos
    Vereb, Gyorgy
    MABS, 2016, 8 (07) : 1361 - 1370
  • [33] Siplizumab Induces NK Cell Fratricide Through Antibody-Dependent Cell-Mediated Cytotoxicity
    Binder, Christian
    Sellberg, Felix
    Cvetkovski, Filip
    Berg, Stefan
    Berglund, Erik
    Berglund, David
    FRONTIERS IN IMMUNOLOGY, 2021, 12
  • [34] Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody-dependent cell-mediated phagocytosis
    Laengle, Johannes
    Kabiljo, Julijan
    Hunter, Leah
    Homola, Jakob
    Prodinger, Sophie
    Egger, Gerda
    Bergmann, Michael
    JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (01)
  • [35] Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies
    Alexandre Iannello
    Ali Ahmad
    Cancer and Metastasis Reviews, 2005, 24 : 487 - 499
  • [36] Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies
    Iannello, A
    Ahmad, A
    CANCER AND METASTASIS REVIEWS, 2005, 24 (04) : 487 - 499
  • [37] Enhancement of antibody-dependent cell mediated cytotoxicity: a new era in cancer treatment
    Rajasekaran, Narendiran
    Chester, Cariad
    Yonezawa, Atsushi
    Zhao, Xing
    Kohrt, Holbrook E.
    IMMUNOTARGETS AND THERAPY, 2015, 4 : 91 - 100
  • [38] A simplified method for the rapid fluorometric assessment of antibody-dependent cell-mediated cytotoxicity
    Gómez-Román, VR
    Florese, RH
    Patterson, LJ
    Peng, B
    Venzon, D
    Aldrich, K
    Robert-Guroff, M
    JOURNAL OF IMMUNOLOGICAL METHODS, 2006, 308 (1-2) : 53 - 67
  • [39] Overcoming chemoresistance of small-cell lung cancer through stepwise HER2-targeted antibody-dependent cell-mediated cytotoxicity and VEGF-targeted antiangiogenesis
    Minami, Toshiyuki
    Kijima, Takashi
    Kohmo, Satoshi
    Arase, Hisashi
    Otani, Yasushi
    Nagatomo, Izumi
    Takahashi, Ryo
    Miyake, Kotaro
    Higashiguchi, Masayoshi
    Morimura, Osamu
    Ihara, Shoichi
    Tsujino, Kazuyuki
    Hirata, Haruhiko
    Inoue, Koji
    Takeda, Yoshito
    Kida, Hiroshi
    Tachibana, Isao
    Kumanogoh, Atsushi
    SCIENTIFIC REPORTS, 2013, 3
  • [40] Lapatinib Enhances Herceptin-mediated Antibody-dependent Cellular Cytotoxicity by Up-regulation of Cell Surface HER2 Expression
    Maruyama, Takanori
    Mimura, Kousaku
    Izawa, Shinichiro
    Inoue, Ayako
    Shiba, Shugo
    Watanabe, Mitsuaki
    Kawaguchi, Yoshihiko
    Inoue, Masayuki
    Nogata, Hisashi
    Inoue, Shingo
    Fujii, Hideki
    Kono, Koji
    ANTICANCER RESEARCH, 2011, 31 (09) : 2999 - 3005