Overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in glioblastoma as well as breast, gastric, lung, colorectal, and pancreatic cancers. Its expression is associated with poor clinical outcomes. Anti-HER2 antibodies have provided significant survival benefits to patients with HER2-overexpressing breast and gastric cancers. We recently developed an anti-HER2 monoclonal antibody (mAb), H2Mab-19 (IgG2b, kappa), by immunizing mice with the extracellular domain of HER2, which is expressed in LN229 glioblastoma cells. In this study, we investigated the antitumor activity of H2Mab-19 in an LN229 glioblastoma xenograft model. H2Mab-19 showed high binding affinity (KD: 1.1 × 10−8 M) against LN229 cells. Furthermore, H2Mab-19 significantly reduced tumor development in an LN229 xenograft. These results suggest that treatment with H2Mab-19 may be a useful therapy for patients with HER2-expressing glioblastomas.
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References
1.
DeAngelisLM: Brain tumors. N Engl J Med, 2001; 344:114–123.
2.
KatoY, KuanCT, ChangJ, KanekoMK, AyrissJ, PiaoH, ChandramohanV, PegramC, McLendonRE, FredmanP, ManssonJE, and BignerDD: GMab-1, a high-affinity anti-3′-isoLM1/3′,6′-isoLD1 IgG monoclonal antibody, raised in lacto-series ganglioside-defective knockout mice. Biochem Biophys Res Commun, 2010; 391:750–755.
3.
ShenL, LiH, BinS, LiP, ChenJ, GuH, and YuanW: The efficacy of third generation antiHER2 chimeric antigen receptor T cells in combination with PD1 blockade against malignant glioblastoma cells. Oncol Rep, 2019; 42:1549–1557.
4.
MiglioriniD, DietrichPY, StuppR, LinetteGP, PoseyADJr., and JuneCH: CAR T-cell therapies in glioblastoma: A first look. Clin Cancer Res, 2018; 24:535–540.
5.
SchneiderJR, KwanK, and BoockvarJA: Use of HER2-specific chimeric antigen receptor-modified virus-specific T cells as a potential therapeutic for progressive HER2-positive glioblastoma. Neurosurgery, 2017; 81:N42–N43.
ZhangL, RenJ, ZhangH, ChengG, XuY, YangS, DongC, FangD, ZhangJ, and YangA: HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo. Oncol Rep, 2016; 36:2689–2696.
8.
HegdeM, MukherjeeM, GradaZ, PignataA, LandiD, NavaiSA, WakefieldA, FousekK, BielamowiczK, ChowKK, BrawleyVS, ByrdTT, KrebsS, GottschalkS, WelsWS, BakerML, DottiG, MamonkinM, BrennerMK, OrangeJS, and AhmedN: Tandem CAR T cells targeting HER2 and IL13Ralpha2 mitigate tumor antigen escape. J Clin Invest, 2016; 126:3036–3052.
9.
TakeiJ, KanekoM, OhishiT, KawadaM, HaradaH, and KatoY: H2Mab-19, an anti-human epidermal growth factor receptor 2 monoclonal antibody exerts antitumor activity in mouse oral cancer xenografts. Exp Ther Med, 2020; 20:846–853.
10.
ItaiS, FujiiY, KanekoMK, YamadaS, NakamuraT, YanakaM, SaidohN, ChangYW, HandaS, TakahashiM, SuzukiH, HaradaH, and KatoY: H2Mab-77 is a sensitive and specific anti-HER2 monoclonal antibody against breast cancer. Monoclon Antib Immunodiagn Immunother, 2017; 36:143–148.
11.
KatoY, KunitaA, AbeS, OgasawaraS, FujiiY, OkiH, FukayamaM, NishiokaY, and KanekoMK: The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC rather than via its neutralizing activity. Oncotarget, 2015; 6:36003–36018.
12.
HowladerN, AltekruseSF, LiCI, ChenVW, ClarkeCA, RiesLA, and CroninKA: US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst, 2014; 106:dju055.
13.
SlamonDJ, ClarkGM, WongSG, LevinWJ, UllrichA, and McGuireWL: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 1987; 235:177–182.
14.
XieS, ZhangH, WangX, GeQ, and HuJ: The relative efficacy and safety of targeted agents used in combination with chemotherapy in treating patients with untreated advanced gastric cancer: A network meta-analysis. Oncotarget, 2017; 8:26959–26968.
15.
LambertJM, and ChariRV: Ado-trastuzumab Emtansine (T-DM1): An antibody-drug conjugate (ADC) for HER2-positive breast cancer. J Med Chem, 2014; 57:6949–6964.
16.
ValabregaG, MontemurroF, and AgliettaM: Trastuzumab: Mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol, 2007; 18:977–984.
17.
Amiri-KordestaniL, WedamS, ZhangL, TangS, TilleyA, IbrahimA, JusticeR, PazdurR, and CortazarP: First FDA approval of neoadjuvant therapy for breast cancer: Pertuzumab for the treatment of patients with HER2-positive breast cancer. Clin Cancer Res, 2014; 20:5359–5364.
18.
SlamonDJ, Leyland-JonesB, ShakS, FuchsH, PatonV, BajamondeA, FlemingT, EiermannW, WolterJ, PegramM, BaselgaJ, and NortonL: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med, 2001; 344:783–792.
19.
SwainSM, KimSB, CortesJ, RoJ, SemiglazovV, CamponeM, CiruelosE, FerreroJM, SchneeweissA, KnottA, ClarkE, RossG, BenyunesMC, and BaselgaJ: Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): Overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol, 2013; 14:461–471.
20.
DoiT, ShitaraK, NaitoY, ShimomuraA, FujiwaraY, YonemoriK, ShimizuC, ShimoiT, KubokiY, MatsubaraN, KitanoA, JikohT, LeeC, FujisakiY, OgitaniY, YverA, and TamuraK: Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: A phase 1 dose-escalation study. Lancet Oncol, 2017; 18:1512–1522.
21.
NakadaT, SugiharaK, JikohT, AbeY, and AgatsumaT: The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy. Chem Pharm Bull (Tokyo), 2019; 67:173–185.
22.
KanekoMK, YamadaS, ItaiS, and KatoY: Development of an anti-HER2 monoclonal antibody H2Mab-139 against colon cancer. Monoclon Antib Immunodiagn Immunother, 2018; 37:59–62.
23.
YamadaS, ItaiS, NakamuraT, ChangYW, HaradaH, SuzukiH, KanekoMK, and KatoY: Establishment of H2Mab-119, an anti-human epidermal growth factor receptor 2 monoclonal antibody, against pancreatic cancer. Monoclon Antib Immunodiagn Immunother, 2017; 36:287–290.
24.
KatoY, and KanekoMK: A cancer-specific monoclonal antibody recognizes the aberrantly glycosylated podoplanin. Sci Rep, 2014; 4:5924.
25.
OgasawaraS, KanekoMK, and KatoY: LpMab-19 recognizes sialylated O-glycan on Thr76 of human podoplanin. Monoclon Antib Immunodiagn Immunother, 2016; 35:245–253.
26.
RobertsM, SevastouI, ImaizumiY, MistryK, TalmaS, DeyM, GartlonJ, OchiaiH, ZhouZ, AkasofuS, TokuharaN, OgoM, AoyamaM, AoyagiH, StrandK, SajediE, AgarwalaKL, SpidelJ, AlboneE, HorieK, StaddonJM, and de SilvaR: Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer's disease. Acta Neuropathol Commun, 2020; 8:13.
27.
WangY, MengY, ZhangS, WuH, YangD, NieC, and HuQ: Phenformin and metformin inhibit growth and migration of LN229 glioma cells in vitro and in vivo. Onco Targets Ther, 2018; 11:6039–6048.
