The kit is shipped at ambient temperature (10-30°C) and should be stored at 2-8°C for long term storage. Keep away from heat or direct sunlight. The strips of microtiter plate are stable up to the expiry date of the kit in the broken, but tightly closed bag when stored at 2-8°C.
Trastuzumab is a recombinant humanized IgG1 monoclonal antibody against the HER-2 receptor, a member of the epidermal growth factor receptors which is a photo-oncogene. Over-expressed in breast tumour cells, HER-2 overamplifies the signal provided by other receptors of the HER family by forming heterodimers. The HER-2 receptor is a transmembrane tyrosine kinase receptor that consists of an extracellular ligand-binding domain, a transmembrane region, and an intracellular or cytoplasmic tyrosine kinase domain. It is activated by the formation of homodimers or heterodimers with other EGFR proteins, leading to dimerization and autophosphorylation and/or transphosphorylation of specific tyrosine residues in EGFR intracellular domains. Further downstream molecular signalling cascades are activated, such as the Ras/Raf/mitogen-activated protein kinase (MAPK), the phosphoinositide 3-kinase/Akt, and the phospholipase Cγ (PLCγ)/protein kinase C (PKC) pathways that promote cell growth and survival and cell cycle progression. Due to upregulation of HER-2 in tumour cells, hyperactivation of these signalling pathways and abnormal cell proliferation is observed. Trastuzumab binds to the extracellular ligandbinding domain and blocks the cleavage of the extracellular domain of HER-2 to induce its antibody-induced receptor downmodulation, and subsequently inhibits HER-2-mediated intracellular signalling cascades. Inhibition of MAPK and PI3K/Akt pathways lead to an increase in cell cycle arrest, and the suppression of cell growth and proliferation. Trastuzumab also mediates the activation of antibody-dependent cell-mediated cytotoxicity (ADCC) by attracting the immune cells, such as natural killer (NK) cells, to tumour sites that overexpress HER-2. Intrinsic trastuzumab resistance has been noted for some patients with HER-2 positive breast cancer. Mechanisms involving trastuzumab resistance include deficiency of phosphatase and tensin homologue and activation of phosphoinositide 3- kinase, and the overexpression of other surface receptors, such as insulin-like growth factor.
Therapeutic drug monitoring (TDM) is the clinical practice of measuring specific drugs at designated intervals to maintain a constant concentration in a patient's bloodstream, thereby optimizing individual dosage regimens. The indications for drug monitoring include efficacy, compliance, drug-drug interactions, toxicity avoidance, and therapy cessation monitoring. Additionally, TDM can help to identify problems with medication compliance among noncompliant patient cases.
Biologic medicinal products (biologics) have transformed treatment landscapes worldwide for patients with haematological or solid malignancies with the 21st century. Today, as data exclusivity periods of first wave biologics approach expiration/have expired, several biosimilar products (i.e., biologics that are considered to be similar in terms of quality, safety and efficacy to an approved 'reference' biologic) are being developed or have already been approved for human use.
Like all biologics, biosimilars are structurally complex proteins that are typically manufactured using genetically engineered animal, bacterial or plant cell culture systems. As a consequence of this molecular complexity and the proprietary nature of the manufacturing process, which will inevitably result in the use of different host cell lines and expression systems as well as related differences in manufacturing conditions, it is not possible to manufacture exact copies of a reference biologic.
When administered to patients, all therapeutic proteins have the potential to induce an unwanted immune response (i.e., to stimulate the formation of antidrug antibodies [ADAs]). The impact of immune responses can range from no apparent effect to changes in pharmacokinetics, loss of effect and serious adverse events. Furthermore, the immunogenicity profile of a biologic can be significantly altered by even small differences in its manufacturing process that are accompanied by a change in product attributes, as well as differences in dosing schedules, administration routes or patient populations.