Trastuzumab (Anti-Human HER2, Humanized Antibody)
(Synonyms: 曲妥珠单抗; Anti-Human HER2, Humanized Antibody) 目录号 : GC34215
曲妥珠单抗是一种针对 HER2 的完全人源化单克隆抗体，它结合受体的外部结构域，并通过抗体依赖性细胞毒性、减少细胞外结构域脱落、抑制二聚化和可能的受体下调来发挥作用。
Cas No.:180288-69-1
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
-
Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
Breast cancer HER2+ cells BT474 and SKBR3 |
|
Preparation Method |
Cells were seeded on 48-wells plates and were treated 24h later with indicated doses of each drug (MZ1 and trastuzumab), alone or in combination. Cell medium was replaced at 72h with MTT solution for 45min at 37℃. |
|
Reaction Conditions |
25-100nM MZ1, 10nM trastuzumab, 25-100nM MZ1+trastuzumab |
|
Applications |
MZ1 showed the highest antiproliferative effect. Trastuzumab combined with MZ1 induced a more profound antiproliferative effect than the administration of single agents in both BT474 and SKBR3 cells. A synergistic interaction between trastuzumab and MZ1 in BT474 cells and an additive interaction in SKBR3 cells was observed. |
| Animal experiment [2]: | |
|
Animal models |
Female BALB/c nude mice, 4-6 weeks |
|
Preparation Method |
Xenografts were used for the experiments once the tumor volume reached about 150-200mm3. Mice were randomly assigned to different groups as follows: (i) vehicle; (ii) trastuzumab 10mg/kg twice weekly of intraperitoneal injection; (iii) AZD5438 20mg/kg daily by oral gavage; (iv) AZD5438+trastuzumab, for 3 weeks. Experiments were ended once the tumor volume surpassed 1500mm3 or mouse weight loss reached 20%. |
|
Dosage form |
10mg/kg trastuzumab, 20mg/kg AZD5438 |
|
Applications |
Trastuzumab exerted antitumor effects in ERBB2-positive AFPGC PDX models. Statistically significant differences were also present in the tumor volume between the group treated with AZD5438 combined with trastuzumab and those treated with AZD5438 or trastuzumab alone in ERBB2 and CCNE1 co-amplified PDX models, but the results were not observed in CCNE1 non-amplified PDX models. |
|
References: [1]. Noblejas-López MDM, Nieto-Jiménez C, et al. MZ1 co-operates with trastuzumab in HER2 positive breast cancer. J Exp Clin Cancer Res. 2021 Mar 19;40(1):106. [2]. Lu J, Ding Y, et al. Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets. Nat Commun. 2021;12(1):3946. Published 2021 Jun 24. doi:10.1038/s41467-021-24170-0 |
|
Trastuzumab is a fully humanized monoclonal antibody directed at HER2 which binds the external domain of the receptor and exerts its action via a combination of antibody-dependent cytotoxicity, reduced shedding of the extracellular domain, inhibition of dimerization and possibly receptor downregulation[1,2]. Trastuzumab is used as a standard treatment for breast and metastatic gastric cancer when the cancer cells overexpress HER2[3].
Trastuzumab combined with MZ1 significantly decreased cell proliferation, the formation of three-dimensional structures and cellular invasion compared to either of the drugs alone[4]. Trastuzumab treated HER2-overexpressing breast cancer cell lines results in induction of p27KIP1 and the Rb-related protein, p130, which in turn significantly reduces the number of cells undergoing S-phase. A number of other phenotypic changes are observed in vitro as a consequence of trastuzumab binding to HER2-overexpressing cells[5]. Trastuzumab-dendrimer-fluorine drug delivery system is a new form of trastuzumab to treat breast cancer cells in vitro. The potential of Trastuzumab-dendrimer-fluorine drug delivery system is more efficient than trastuzumab alone[6]
Trastuzumab causes a significant growth inhibition of the outgrowth of macroscopic JIMT-1 xenograft tumors in both nude and SCID mice[7]. The administration of MZ1 and trastuzumab induced a reduction in tumor progression, while individual treatments failed to do so[4]
References:
[1]. Ning G, Zhu Q, et al. A novel treatment strategy for lapatinib resistance in a subset of HER2-amplified gastric cancer. BMC Cancer. 2021;21(1):923. Published 2021 Aug 16. doi:10.1186/s12885-021-08283-9
[2]. Okines AF, Cunningham D. Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer. Therap Adv Gastroenterol. 2012 Sep;5(5):301-18.
[3]. Sarosiek T, Morawski P. Trastuzumab and its biosimilars [Trastuzumab and its biosimilars]. Pol Merkur Lekarski. 2018 May 25;44(263):253-257. Polish.
[4]. Noblejas-López MDM, Nieto-Jiménez C, et al. MZ1 co-operates with trastuzumab in HER2 positive breast cancer. J Exp Clin Cancer Res. 2021 Mar 19;40(1):106.
[5]. Sliwkowski MX, Lofgren JA, et al. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol. 1999 Aug;26(4 Suppl 12):60-70.
[6]. Bartusik-Aebisher D, Chrzanowski G, et al. An analytical study of Trastuzumab-dendrimer-fluorine drug delivery system in breast cancer therapy in vitro. Biomed Pharmacother. 2021 Jan;133:111053.
[7]. Barok M, Isola J, et al. Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance. Mol Cancer Ther. 2007 Jul;6(7):2065-72.
曲妥珠单抗是一种针对 HER2 的完全人源化单克隆抗体，它结合受体的外部结构域，并通过抗体依赖性细胞毒性、减少细胞外结构域脱落、抑制二聚化和可能的受体下调来发挥作用[1,2]。当癌细胞过度表达 HER2[3] 时，曲妥珠单抗被用作乳腺癌和转移性胃癌的标准治疗方法。
与单独使用任何一种药物相比，曲妥珠单抗联合 MZ1 可显着降低细胞增殖、三维结构的形成和细胞侵袭[4]。曲妥珠单抗处理的 HER2 过表达乳腺癌细胞系导致 p27KIP1 和 Rb 相关蛋白 p130 的诱导，这反过来显着减少了经历 S 期的细胞数量。由于曲妥珠单抗与 HER2 过表达细胞结合，在体外观察到许多其他表型变化[5]。曲妥珠单抗-树枝状大分子-氟药物递送系统是一种新形式的曲妥珠单抗，可在体外治疗乳腺癌细胞。曲妥珠单抗-树枝状大分子-氟药物递送系统的潜力比单独使用曲妥珠单抗更有效[6]
曲妥珠单抗可显着抑制裸鼠和 SCID 小鼠肉眼可见的 JIMT-1 异种移植肿瘤的生长[7]。 MZ1 和曲妥珠单抗的给药诱导了肿瘤进展的减缓，而单独的治疗则未能做到这一点[4]
| Cas No. | 180288-69-1 | SDF | |
| 别名 | 曲妥珠单抗; Anti-Human HER2, Humanized Antibody | ||
| Canonical SMILES | [Trastuzumab] | ||
| 分子式 | C6470H10012N1726O2013S42 | 分子量 | 145145.09 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 0.0069 mL | 0.0344 mL | 0.0689 mL |
| 5 mM | 0.0014 mL | 0.0069 mL | 0.0138 mL |
| 10 mM | 0.0007 mL | 0.0034 mL | 0.0069 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity
Cancer Sci 2016 Jul;107(7):1039-46.PMID:27166974DOI:10.1111/cas.12966.
Antibody-drug conjugates deliver anticancer agents selectively and efficiently to tumor tissue and have significant antitumor efficacy with a wide therapeutic window. DS-8201a is a human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate prepared using a novel linker-payload system with a potent topoisomerase I inhibitor, exatecan derivative (DX-8951 derivative, DXd). It was effective against Trastuzumab emtansine (T-DM1)-insensitive patient-derived xenograft models with both high and low HER2 expression. In this study, the bystander killing effect of DS-8201a was evaluated and compared with that of T-DM1. We confirmed that the payload of DS-8201a, DXd (1), was highly membrane-permeable whereas that of T-DM1, Lys-SMCC-DM1, had a low level of permeability. Under a coculture condition of HER2-positive KPL-4 cells and negative MDA-MB-468 cells in vitro, DS-8201a killed both cells, whereas T-DM1 and an antibody-drug conjugate with a low permeable payload, anti-HER2-DXd (2), did not. In vivo evaluation was carried out using mice inoculated with a mixture of HER2-positive NCI-N87 cells and HER2-negative MDA-MB-468-Luc cells by using an in vivo imaging system. In vivo, DS-8201a reduced the luciferase signal of the mice, indicating suppression of the MDA-MB-468-Luc population; however, T-DM1 and anti-HER2-DXd (2) did not. Furthermore, it was confirmed that DS-8201a was not effective against MDA-MB-468-Luc tumors inoculated at the opposite side of the NCI-N87 tumor, suggesting that the bystander killing effect of DS-8201a is observed only in cells neighboring HER2-positive cells, indicating low concern in terms of systemic toxicity. These results indicated that DS-8201a has a potent bystander effect due to a highly membrane-permeable payload and is beneficial in treating tumors with HER2 heterogeneity that are unresponsive to T-DM1.
Pertuzumab plus Trastuzumab plus docetaxel for metastatic breast cancer
N Engl J Med 2012 Jan 12;366(2):109-19.PMID:22149875DOI:10.1056/NEJMoa1113216.
Background: The anti-human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody Trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of Trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer. Methods: We randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive placebo plus Trastuzumab plus docetaxel (control group) or pertuzumab plus Trastuzumab plus docetaxel (pertuzumab group) as first-line treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. The primary end point was independently assessed progression-free survival. Secondary end points included overall survival, progression-free survival as assessed by the investigator, the objective response rate, and safety. Results: The median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001). The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus Trastuzumab plus docetaxel. The safety profile was generally similar in the two groups, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group. Conclusions: The combination of pertuzumab plus Trastuzumab plus docetaxel, as compared with placebo plus Trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT00567190.).
Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial
J Clin Oncol 2023 Feb 1;41(4):816-825.PMID:36379002DOI:10.1200/JCO.22.00575.
Purpose: To investigate efficacy and safety of Trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-low gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: Patients with locally advanced or metastatic HER2-low (cohort 1, immunohistochemistry 2+/in situ hybridization-negative; cohort 2, immunohistochemistry 1+) gastric/GEJ adenocarcinoma treated with at least two prior regimens, including fluoropyrimidine and platinum, but anti-HER2 therapy naive, received T-DXd 6.4 mg/kg intravenously once every 3 weeks. The primary end point was confirmed objective response rate by independent central review. Results: Among 21 patients enrolled in cohort 1 and 24 enrolled in cohort 2, 19 and 21 patients, respectively, had central HER2 confirmation, received T-DXd, and had measurable tumors at baseline. The confirmed objective response rate was 26.3% (95% CI, 9.1 to 51.2) from five partial responses in cohort 1 and 9.5% (95% CI, 1.2 to 30.4) from two partial responses in cohort 2. Thirteen patients (68.4%) in cohort 1 and 12 (60.0%) in cohort 2 experienced reduced tumor size. The median overall survival was 7.8 months (95% CI, 4.7 to nonevaluable) in cohort 1 and 8.5 months (95% CI, 4.3 to 10.9) in cohort 2; the median progression-free survival was 4.4 months (95% CI, 2.7 to 7.1) and 2.8 months (95% CI, 1.5 to 4.3), respectively. The most common grade ≥ 3 treatment-emergent adverse events in cohorts 1 and 2 were anemia (30.0% and 29.2%), decreased neutrophil count (25.0% and 29.2%), and decreased appetite (20.0% and 20.8%). Drug-related interstitial lung disease/pneumonitis occurred in one patient in each cohort (grade 1 or 2). No drug-related deaths occurred. Conclusion: This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/GEJ adenocarcinoma.
Combining CD47 blockade with Trastuzumab eliminates HER2-positive breast cancer cells and overcomes Trastuzumab tolerance
Proc Natl Acad Sci U S A 2021 Jul 20;118(29):e2026849118.PMID:34257155DOI:10.1073/pnas.2026849118.
Trastuzumab, a targeted anti-human epidermal-growth-factor receptor-2 (HER2) monoclonal antibody, represents a mainstay in the treatment of HER2-positive (HER2+) breast cancer. Although Trastuzumab treatment is highly efficacious for early-stage HER2+ breast cancer, the majority of advanced-stage HER2+ breast cancer patients who initially respond to Trastuzumab acquire resistance to treatment and relapse, despite persistence of HER2 gene amplification/overexpression. Here, we sought to leverage HER2 overexpression to engage antibody-dependent cellular phagocytosis (ADCP) through a combination of Trastuzumab and anti-CD47 macrophage checkpoint immunotherapy. We have previously shown that blockade of CD47, a surface protein expressed by many malignancies (including HER2+ breast cancer), is an effective anticancer therapy. CD47 functions as a "don't eat me" signal through its interaction with signal regulatory protein-α (SIRPα) on macrophages to inhibit phagocytosis. Hu5F9-G4 (magrolimab), a humanized monoclonal antibody against CD47, blocks CD47's "don't eat me" signal, thereby facilitating macrophage-mediated phagocytosis. Preclinical studies have shown that combining Hu5F9-G4 with tumor-targeting antibodies, such as rituximab, further enhances Hu5F9-G4's anticancer effects via ADCP. Clinical trials have additionally demonstrated that Hu5F9-G4, in combination with rituximab, produced objective responses in patients whose diffuse large B cell lymphomas had developed resistance to rituximab and chemotherapy. These studies led us to hypothesize that combining Hu5F9-G4 with Trastuzumab would produce an anticancer effect in antibody-dependent cellular cytotoxicity (ADCC)-tolerant HER2+ breast cancer. This combination significantly suppressed the growth of ADCC-tolerant HER2+ breast cancers via Fc-dependent ADCP. Our study demonstrates that combining Trastuzumab and Hu5F9-G4 represents a potential new treatment option for HER2+ breast cancer patients, even for patients whose tumors have progressed after Trastuzumab.
Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity-From Bench to Bedside
Biomedicines 2020 Dec 7;8(12):577.PMID:33297351DOI:10.3390/biomedicines8120577.
Background: Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, is considered a standard treatment in addition to chemotherapy in the adjuvant setting for HER2/neu-positive breast cancer, yet its impact on fertility and ovarian reserve remains obscure. We aimed to study the effect of anti-HER2/neu on chemotherapy-induced ovarian toxicity in both clinical and preclinical settings. Methods: We prospectively enrolled breast cancer patients below the age of 42 years who were treated with chemotherapy with or without Trastuzumab into the study. Anti-Müllerian hormone (AMH) was measured 6 and 12 months post-chemotherapy as an ovarian reserve indicator. In the animal model, pubertal mice were injected with cyclophosphamide or paclitaxel with or without anti-HER2/neu, or saline, and sacrificed 1 week or 3 months later. Ovarian apoptosis, proliferation and vascularity were measured by immunohistochemistry and ovarian reserve was measured by morphometric analysis and serum-AMH. Results: Thirty-three patients with early breast cancer were enrolled into the study. Nineteen patients had HER2/neu negative cancer and were treated with chemotherapy and 14 had HER2/neu positive cancer and were treated with chemotherapy and Trastuzumab. In all patients, AMH levels declined to undetectable values immediately post-treatment, but regained for 57.1% of the HER2/neu positive cohort and 36.8% of the negative cohort (p < 0.05). In the preclinical setting, anti-HER2/neu antibody, in combination with chemotherapy, displayed lessened ovarian and vascular damage. Conclusions: Our results indicate that Trastuzumab may alleviate chemotherapy-induced ovarian toxicity that may be mediated via its effect on ovarian vasculature.