Trastuzumab

Specification

• Cat#: THA-0013
• Product Name: Trastuzumab
• Description: Trastuzumab is a monoclonal anti-human epidermal growth factor receptor 2 protein antibody used to treat HER2-positive breast, gastroesophageal, and gastric cancers.
• Sequences: Anti-HER2 Light chain (1 and 2): DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Anti-HER2 Heavy chain (1 and 2): EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
• Molecular Weight: 145531.5 Da
• Source: CHO
• Introduction: Produced in CHO cell cultures, trastuzumab is a recombinant IgG1 kappa, humanized monoclonal antibody that selectively binds with high affinity in a cell-based assay (Kd = 5 nM) to the extracellular domain of the human epidermal growth factor receptor protein (HER2). It is used as a treatment of human epidermal growth factor receptor (HER)-2+ metastatic breast cancer, where there is a proven amplification of the HER-2 oncogene or over-expression of the HER-2 protein in tumours. It is suggested that the overexpression or gene amplification of HER2 has been found in about 20–30% of breast cancers and elevated activation of HER2 triggers multiple downstream pathways leading to abnormal proliferation of cancer cells. Trastuzumab binds to HER2 and suppresses cancer cell growth, proliferation, and survival directly and indirectly. In December 2017, FDA approved OGIVRI (trastuzumab-dkst) as a biosimilar to Herceptin (trastuzumab) for the treatment of patients with breast or metastatic stomach cancer (gastric or gastroesophageal junction adenocarcinoma) whose tumors overexpress the HER2 gene (HER2+). It displays biosimilar properties as Herceptin according to clinical data. While Ogivri is the first biosimilar approved in the U.S. for the treatment of breast cancer or stomach cancer, it is the second biosimilar approved in the U.S. for the treatment of cancer. Herzuma (trastuzumab-pkrb) is a biosimilar drug approved in December 2018 for the treatment of HER2-overexpressing breast cancer. KANJINTI (trastuzumab-anns) is another biosimilar approved by the FDA in June 2019. ONTRUZANT, another biosimilar of Herceptin, was approved by Health Canada in February 2022. In November 2023, trastuzumab was also approved by the EMA under the brand name Herwenda.
• Purity: >99% by SDS-Page and HPLC analysis
• Formula: C6470H10012N1726O2013S42
• Appearance: Solid
• Endotoxin Level: < 0.001 EU/μg of the protein by the LAL method

Pharmaceutical Information

• Pharmacodynamics: Trastuzumab exerts an antitumour activity and is used in the treatment of HER2-positive breast cancer. HER2 protein overexpression is observed in 20%-30% of primary breast cancers thus HER2 presents as a useful therapeutic target for the treatment of breast cancers. Trastuzumab has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumour cells that overexpress HER2. It works as a mediator of antibody-dependent cellular cytotoxicity, where it binds as an antibody to cells over-expressing HER2, leading to preferential cell death. Trastuzumab was also shown to inhibit angiogenesis of tumor cells in vivo. Higher doses and longer dosing intervals show no significant benefit over standard dose schedules. In patients with HER2 positive solid tumours, trastuzumab did not exert any clinically significant QTc interval duration.
• Targets: Receptor tyrosine-protein kinase erbB-2