Trastuzumab

MCE 国际站：Trastuzumab

产品活性：Trastuzumab 是一种人源化 IgG1 单克隆抗体，其以高亲和力与 HER2 选择性结合。Trastuzumab 可用于 HER2 阳性转移性乳腺癌和 HER2 阳性胃癌的研究。

研究领域：JAK/STAT Signaling | Protein Tyrosine Kinase/RTK | Antibody-drug Conjugate/ADC Related

In Vitro: Treatment of HER2-overexpressing breast cancer cell lines with Trastuzumab 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. Interaction of Trastuzumab with the human immune system via its human immunoglobulin G1 Fc domain may potentiate its antitumor activities. in vitro studies demonstrate that Trastuzumab is very effective in mediating antibody-dependent cell-mediated cytotoxicity against HER2-overexpressing tumor targets. Trastuzumab consists of two antigen-specific sites that bind to the juxtamembrane portion of the extracellular domain of the HER2 receptor and that prevent the activation of its intracellular tyrosine kinase. Trastuzumab recruits immune effector cells that are responsible for antibody-dependent cytotoxicity. The presence of Trastuzumab IgG significantly increases killing of all breast cancer cell lines. The ADCC activity of PBMCs evoked by Trastuzumab is equally strong against Trastuzumab-sensitive (SKBR-3) or Trastuzumab-resistant (JIMT-1) breast cancer cells, with dose-dependent cell death reaching 50–60% killing at an effector/target ratio of 60:1.

In Vivo: Trastuzumab treatment of mouse xenograft models results in marked suppression of tumor growth. When given in combination with standard cytotoxic chemotherapeutic agents, Trastuzumab treatment generally results in statistically superior antitumor efficacy compared with either agent given alone. Trastuzumab causes a significant growth inhibition of the outgrowth of macroscopic JIMT-1 xenograft tumors in both nude and SCID mice.

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