Trastuzumab

• CAS: 180288-69-1
• Catalog Number: ACM180288691
• Category: Main Products
• Molecular Weight: 36.46094;g/mol
• Molecular Formula: ClH
• IUPAC Name: chlorane
• Canonical SMILES: Cl
• InChI Key: VEXZGXHMUGYJMC-UHFFFAOYSA-N
• EC Number: 231-595-7
• UN Number: 1050

Case Study

The Application of Trastuzumab in Cholangiocarcinoma Treatment

Panaampon J, et al. International Immunopharmacology, 2024, 138, 112612.

Analysis: Human epidermal growth factor receptor 2 (HER2) expression was observed in seven liver-fluke-associated cholangiocarcinoma (CCA) cell lines, albeit at low levels. Despite this weak positivity, Trastuzumab exhibited significant inhibitory effects on CCA cells, as confirmed through multiple in vitro assays. An MTT assay revealed a direct suppression of CCA cell growth by Trastuzumab. Moreover, its efficacy extended beyond simple growth inhibition, engaging immune mechanisms such as antibody-dependent cytotoxicity (ADCC) and antibody-dependent cell phagocytosis (ADCP) via natural killer (NK) cells and macrophages, respectively. Complement-dependent cytotoxicity (CDC) activity was also verified through rabbit serum experiments.
Further testing in in vivo models using patient-derived cell xenografts (PDX) showed that Trastuzumab effectively inhibited tumor growth, highlighting its therapeutic potential even in cases of weak HER2 expression. These findings suggest that Trastuzumab's multifaceted mechanism of action makes it a promising candidate for CCA immunotherapy, where treatment options are currently limited.
Conclusion: Trastuzumab, although primarily used for HER2-positive breast and gastric cancers, has demonstrated potential in the treatment of liver-fluke-associated CCA. Its ability to suppress CCA tumor growth via multiple mechanisms, even in weakly HER2-positive cells, positions Trastuzumab as a potential therapeutic agent for this aggressive cancer.

Trastuzumab Used in the Development of a New Radiotracer with the [52Mn]Mn Isotope

Toàn NM, et al. J. Med. Chem. 2024, 67, 10, 8261-8270,

Trastuzumab can be used to develop a novel radiotracer in conjunction with the long-lived isotope [52Mn]Mn to enable selection and monitoring of HER2-targeted therapy. The novel Mn(II) chelator BPPA was converted into a bifunctional chelator (BFC), conjugated to trastuzumab, and labeled with the [52Mn]Mn isotope. The BPPA-trastuzumab conjugate showed approximately two orders of magnitude improvement in the labeling efficiency of [52Mn]Mn compared to DOTA-GA-trastuzumab.
[52Mn]Mn-BPPA-trastuzumab and [52Mn]Mn-DOTA-GA-trastuzumab were prepared as follows:
[52Mn]Mn-BPPA-trastuzumab: 10-15 µL of 21 mg/ml BPPA-trastuzumab solution was added to a mixture of [52Mn]MnCl2 solution consisting of 0.1 M HCl (50 µL, 16-26 MBq), 0.1 M pH 7 HEPES (43.5 µL), and 0.5 M NaOH (10 µL). The reaction mixture was incubated at room temperature for 15 minutes. The radiochemical purity (RCP) was determined by thin layer chromatography on iTLC-SG using 0.1 M citric acid. The reaction mixture was then divided into three portions and diluted to 200 µL with saline.
[52Mn]Mn-DOTA-GA-Trastuzumab: Add 35-40 µL of a 21 mg/ml DOTA-GA trastuzumab solution to a mixture containing [52Mn]MnCl2 consisting of 0.1 M HCl (32-36 MBq), 0.1 M NaOAc (65 µL), and 0.5 M NaOH (7-10 µL). Incubate the reaction mixture at room temperature for 15 minutes. RCP is determined by thin layer chromatography on iTLC-SG, also using 0.1 M citric acid. Finally, divide the reaction mixture into three portions and dilute to 200 µL with saline.