Dinutuximab is a specialized medication used to treat certain cancers, particularly in children. This article explains what dinutuximab is, how it works, and its specific application in fighting cancer.
Understanding Dinutuximab
Dinutuximab is a type of targeted therapy, a monoclonal antibody. Monoclonal antibodies are engineered proteins designed to identify and attach to specific targets in the body, much like a key fitting into a lock. These antibodies are created in a laboratory to mimic the natural antibodies produced by the immune system. Once they bind to their specific targets, they can either block the target’s function or mark the cells for destruction by the body’s immune defenses.
Dinutuximab is a chimeric monoclonal antibody, meaning it combines components from both mouse and human antibodies. This design helps to reduce the likelihood of the human body rejecting the antibody as foreign. Its general role in cancer treatment involves specifically recognizing and attaching to cancer cells, helping the immune system eliminate them.
How Dinutuximab Fights Cancer
Dinutuximab specifically targets a sugar molecule called disialoganglioside GD2, which is found in high amounts on the surface of certain cancer cells, such as neuroblastoma. GD2 is a glycolipid, a type of fat molecule with attached sugar chains, that is found in limited quantities on normal tissues like neurons and skin melanocytes. Its high expression on cancer cells makes it an effective target for therapeutic intervention.
When dinutuximab binds to GD2 on the surface of cancer cells, it alerts the immune system to destroy these cells. One way this happens is through antibody-dependent cell-mediated cytotoxicity (ADCC). In ADCC, immune effector cells, like natural killer (NK) cells, recognize antibody-coated cancer cells and release substances such as perforin and granzymes, inducing programmed cell death.
Another mechanism is complement-dependent cytotoxicity (CDC). The complement system, a group of blood proteins, activates when the antibody binds, forming a membrane attack complex (MAC). The MAC creates pores in the cancer cell’s membrane, disrupting its integrity and leading to cell lysis, or bursting. Both ADCC and CDC work together to eliminate GD2-expressing cancer cells, providing a targeted approach to fighting the disease.
Treating High-Risk Neuroblastoma
Dinutuximab is primarily used in the treatment of high-risk neuroblastoma, an aggressive childhood cancer that originates from immature nerve cells. This particular form often has a poor prognosis despite intensive initial treatments. Dinutuximab is typically administered to children aged 12 months and older who have completed initial intensive treatments, including chemotherapy, surgery, radiation therapy, and high-dose chemotherapy followed by autologous stem cell rescue.
The medication fits into the overall treatment strategy as a maintenance therapy to help prevent cancer recurrence and improve long-term survival. It is often given in combination with other agents, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (isotretinoin). These combinations aim to further enhance the immune system’s ability to target and eliminate any remaining neuroblastoma cells, including minimal residual disease cells that can persist after initial successful treatments.
Receiving Treatment and Managing Side Effects
Dinutuximab is administered intravenously, directly into a vein through an infusion. The infusion typically lasts 10 to 20 hours and is given over four consecutive days during specific treatment cycles. A complete course of treatment can involve up to five cycles of dinutuximab in combination with other medications.
Close medical supervision is necessary during treatment due to the potential for side effects. One of the most common and significant side effects is severe neuropathic pain, which can occur because GD2 is also present on healthy nerve cells. To manage this pain, intravenous opioid medications, such as morphine sulfate, are administered immediately before, during, and for a few hours after each infusion. Doses or infusion rates may be adjusted as needed.
Other common side effects include fever, an expected immune response, managed with acetaminophen or ibuprofen. Infusion reactions, ranging from mild to severe, may also occur, with symptoms like hives, itching, rash, difficulty breathing, or low blood pressure. Patients receive premedications such as antihistamines and sometimes corticosteroids before the infusion to reduce the risk of these reactions. Medical teams also monitor for capillary leak syndrome, a rare but serious condition causing fluid retention and swelling, and peripheral neuropathy, manifesting as numbness, tingling, or weakness in the limbs. In some cases, if severe side effects like unresponsive pain or motor neuropathy occur, treatment may need to be discontinued.