Monoclonal antibodies (mAbs) and their nomenclature
The foundation of targeted therapy is antibodies synthesized by a single cell clone. The industrial production process includes rodent immunization, the creation of immortal cell lines (hybridomas, often based on Chinese hamster ovary cells), and clone cultivation.
Initially, the drugs consisted of murine protein, which caused severe allergic reactions. Genetic engineering led to the development of humanized antibodies, in which murine genes are replaced with human ones, sharply reducing their allergenicity.
International names of mAbs always end in -mab (monoclonal antibody). The insert before the suffix indicates the origin of the drug:
- -o- (-omab) — murine;
- -xi- (-ximab) — chimeric (murine framework with a human Fc fragment);
- -zu- (-zumab) — humanized;
- -u- (-mumab) — fully human.
Cell receptor blockers (HER2, CD20, EGFR)
Drugs in this group bind to antigens on the cell surface, depriving them of proliferation and survival signals.
- Trastuzumab (Trastuzumab). A humanized antibody against the HER2 receptor. Administered intravenously for breast cancer (often in combination with paclitaxel). A specific severe adverse effect is heart failure.
- Rituximab (Rituximab). The first officially approved chimeric antibody against the CD20 antigen on B-lymphocytes. Effective in chronic lymphocytic leukemia (in combination with cyclophosphamide, doxorubicin, etc.). Due to massive cell death, it can cause severe tumor lysis syndrome within the first 24 hours, as well as infectious complications.
- Cetuximab and Panitumumab. Block the epidermal growth factor receptor (EGFR), which stimulates metastasis and angiogenesis in solid tumors (e.g., in colorectal cancer). Panitumumab is a fully human drug, so it rarely causes infusion reactions, but it can cause acneiform rash and hypomagnesemia.
Angiogenesis inhibitors
A dedicated vascular network is critically essential for tumor growth and metastasis. The main stimulator of this process is vascular endothelial growth factor (VEGF).
- Bevacizumab. A humanized mAb that binds the VEGF factor (ligand) itself, preventing it from activating receptors. Used in colorectal cancer, lung cancer, and breast cancer. Due to its systemic effect on vessels, it can provoke hypertension, thromboembolism (myocardial infarction, stroke), proteinuria, and impair wound healing (up to GI perforation).
- Sorafenib and sunitinib. Belong to small molecules. They act as multikinase inhibitors, directly blocking receptors for VEGF and platelet-derived growth factor (PDGF). Used in renal and hepatic cell carcinoma.
Tyrosine kinase inhibitors and small molecules
Unlike large protein antibodies, small molecules are taken orally and are actively metabolized in the liver by the CYP3A4 enzyme.
- Imatinib. Developed for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Its target is a specific oncoprotein produced due to a mutation (the appearance of the Philadelphia chromosome). Adverse effects: edema syndrome, cytopenias, dyspepsia.
- Gefitinib and erlotinib. Oral EGFR blockers for lung cancer therapy. Can cause rash, diarrhea, and fatal acute respiratory failure.
Clinically important rule: there is a high risk of drug interactions when taking these drugs. For example, grapefruit juice inhibits the CYP3A4 enzyme, which disrupts the breakdown of drugs in the liver and significantly increases their toxicity.
To remember the origin of monoclonal antibodies by their suffixes, use associations: O — mUrine (-omab), U — hUman nature (-mumab), ZU — hUmanized (-zumab), XI — chimeric (like the letter X — crossing of species, -ximab).
Class and exam questions
What is the main difference between targeted therapy and conventional chemotherapy?
Targeted drugs act precisely on specific molecules (targets) of tumor cells, helping the immune system recognize them. Conventional chemotherapy affects all rapidly dividing cells of the body, which causes higher systemic toxicity.
Why might hemodialysis be required during rituximab treatment?
The drug causes rapid and massive destruction of tumor B-lymphocytes, leading to tumor lysis syndrome. This places an acute load on the kidneys from cellular breakdown products and can provoke acute kidney injury.
How does diet affect the intake of oral targeted drugs (imatinib, gefitinib)?
These drugs are metabolized by the hepatic enzyme CYP3A4. Consumption of grapefruit juice blocks this enzyme, which halts the breakdown of the drug in the body and can lead to a dangerous overdose.
What else to study on this topic
- Mechanisms of chemoresistance development upon EGFR pathway activation.
- The role of the Philadelphia chromosome in the pathogenesis of chronic myeloid leukemia.
- Tumor lysis syndrome: pathophysiology and intensive care algorithms.
- Infectious complications secondary to systemic B-lymphocyte suppression.
- Features of drug metabolism by the CYP3A4 cytochrome system and drug interactions.
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