Monoclonal antibody therapies offer a precise, targeted approach to treating various diseases. These laboratory-produced proteins mimic the body’s natural antibodies, which identify and neutralize foreign or harmful substances. Unlike traditional treatments, monoclonal antibodies bind to specific targets, aiming for focused therapeutic effects. This targeted action allows for individualized treatment, promising improved outcomes.
The Design of Monoclonal Antibodies
Monoclonal antibodies are engineered for specificity, originating from a single, cloned immune cell. This ensures all antibodies are identical copies, binding exclusively to a unique antigen. An antigen can be a protein on a cancer cell, a signaling molecule in inflammation, or a component of a virus or bacterium.
The development process begins by exposing immune cells, often from a mouse, to the target antigen. These cells produce antibodies, whose genetic sequences are then harvested. These sequences are inserted into expression systems, like bacteria or mammalian cells, for mass production. To prevent rejection by the human immune system, antibodies are “humanized” or made fully human, replacing mouse structures with human sequences while retaining the binding sites.
Diverse Mechanisms of Action
Monoclonal antibodies exert their therapeutic effects through diverse mechanisms. One common mechanism is blocking, where the antibody prevents a target molecule from interacting with its receptor. For example, some antibodies block growth factors from binding to cancer cells, inhibiting tumor growth. Bevacizumab blocks vascular endothelial growth factor (VEGF), involved in new blood vessel formation for tumors.
Another mechanism involves marking for destruction, where the antibody tags diseased cells for elimination by the body’s immune system. This occurs through processes like antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). In ADCC, the antibody binds to the target cell, signaling immune effector cells like natural killer cells to destroy it. Rituximab, used in some lymphomas, binds to the CD20 protein on B cells, leading to their destruction.
Monoclonal antibodies can also function by delivering payloads directly to target cells. These are known as antibody-drug conjugates (ADCs) or radiolabeled antibodies. A chemotherapy drug, toxin, or radioactive particle is attached to the antibody, which then acts as a “homing device,” delivering the substance to cancer cells while minimizing damage to healthy tissues. Brentuximab vedotin, for instance, delivers a chemotherapy drug to cells expressing the CD30 antigen.
Some monoclonal antibodies work by modulating immune responses, either activating or deactivating specific immune cells or pathways. This is relevant in cancer immunotherapy, where antibodies can block immune checkpoints. Immune checkpoint inhibitors, such as pembrolizumab, prevent cancer cells from “turning off” immune cells, allowing the immune system to attack cancerous cells more effectively. Other antibodies might activate immune cells to fight infections or dampen overactive immune responses in autoimmune conditions.
Applications in Major Diseases
Monoclonal antibody therapies have broad utility in treating a wide array of diseases. In cancer treatment, these antibodies serve as targeted therapies and immunotherapies. They attack cancer cells by binding to specific tumor markers, blocking growth, or signaling the immune system to destroy them. Examples include trastuzumab, which targets the HER2 protein in certain breast and stomach cancers, and rituximab for non-Hodgkin lymphoma by targeting CD20-positive B cells.
For autoimmune diseases, where the immune system mistakenly attacks healthy tissues, monoclonal antibodies modulate the immune response and reduce inflammation. They target specific inflammatory pathways or immune cells. Adalimumab and infliximab treat conditions like rheumatoid arthritis, Crohn’s disease, and psoriasis by inhibiting TNF-alpha. Basiliximab and daclizumab inhibit IL-2 on activated T cells to help prevent kidney transplant rejection.
Monoclonal antibodies also manage infectious diseases. They provide passive immunity by neutralizing viruses or bacteria, preventing them from infecting cells. For example, they have been used for preventing respiratory syncytial virus (RSV) in infants and in some severe COVID-19 cases. These antibodies bind to viral components, blocking entry into host cells or marking them for immune clearance.
Patient Considerations and Side Effects
Patients receive monoclonal antibody therapies through intravenous (IV) infusion or subcutaneous injection. The method and duration depend on the condition, antibody type, and patient health. IV infusions administer the antibody directly into the bloodstream over 30 minutes to several hours, often in an infusion center. Subcutaneous injections are given under the skin and may be administered less frequently.
While well-tolerated, monoclonal antibody therapies can lead to side effects. Infusion-related reactions are common immediate side effects, particularly during the first infusion. Symptoms can include fever, chills, fatigue, headache, nausea, vomiting, diarrhea, rash, and low blood pressure. Healthcare professionals closely monitor patients for these reactions, especially during and immediately after administration, sometimes requiring observation post-treatment.
Due to their action on the immune system, some monoclonal antibodies can increase the risk of infections by suppressing immune functions. Patients may be advised on preventive measures, such as vaccinations or antimicrobial prophylaxis. Specific adverse events can occur depending on the antibody’s target. For instance, antibodies targeting VEGF, like bevacizumab, can lead to high blood pressure, bleeding, poor wound healing, or blood clots. Antibodies targeting EGFR, such as cetuximab, may cause severe skin rashes. Patients are monitored with regular blood tests or scans to detect and manage these issues.