نظرة عامة

Bispecific antibody therapy uses medicines that target diseases in two ways at the same time. It uses specially designed, lab-made proteins called bispecific antibodies.

These medicines come in several forms and can work in different ways. Many are a type of immunotherapy. They help the body's immune system recognize and attack cancer cells. Others block the signals that help cancer cells grow or survive. What makes them unique is their ability to attach to two different proteins at once. Often, one attaches to an immune cell and one to a cancer cell. Bispecific antibody therapies are sometimes called bispecifics or BsAbs.

Several bispecific antibody therapies have been approved by the U.S. Food and Drug Administration (FDA). Most are used to treat blood cancers and cancers of the lymphatic system, such as multiple myeloma, leukemia and lymphoma. A few are approved for solid tumors, including some lung and eye cancers. Others are approved for noncancerous conditions, such as hemophilia and certain eye diseases.

Bispecific antibody therapy may be an option when other treatments stop working. Or it may be used in combination with other treatments to improve results.

Bispecific antibodies versus monoclonal antibodies

Bispecific antibodies are a step up from monoclonal antibodies. Monoclonal antibodies are synthetic substitutes for natural antibodies. They target single proteins on cancer cells, boosting the body's immune response against cancer. But while monoclonal antibodies may work for a time, cancer cells eventually develop other ways to avoid destruction.

Bispecific antibodies have two "arms," so they can interact with two separate targets at once. This makes them powerful tools in fighting cancer cells. Multispecific antibodies also are being developed.

Types

Bispecific antibodies work in different ways depending on how they're designed. There are hundreds in clinical trials, testing more than 60 different target combinations.

Common types include those that:

  • Activate the immune system. Some bispecifics link T cells — key immune cells — directly to cancer cells. T cells help defend the body by attacking harmful cells. Bispecifics that interact with T cells are sometimes called bispecific T cell engagers or BiTE therapies. One arm of the bispecific engages with CD3, a protein complex that activates T cells. The other arm attaches to the cancer cell. This connection activates the T cell to release proteins that kill the cancer cell.
  • Block cell signals. Some bispecifics block two cell signals at once. For example, amivantamab (Rybrevant) blocks two signaling proteins that help lung cancer cells grow: epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET), also known as hepatocyte growth factor receptor. Blocking these signals can help slow or stop tumor growth.
  • Deliver treatment. Some bispecifics being studied use one arm to attach to a cancer cell and the other to bring medicine or radiation directly to that cell. This approach helps deliver treatment precisely where it's needed, which may reduce harm to healthy cells.

Bispecific antibody therapy has several key features that make it an attractive treatment option.

  • Ready-to-use treatment. Bispecifics are "off-the-shelf" medicines. This makes them different from chimeric antigen receptor (CAR)-T cell therapy, which requires a customized manufacturing process.
  • Outpatient care. Most people don't need to stay overnight in a hospital to receive this therapy.
  • Manageable side effects. Side effects such as fever or confusion are usually milder than with other advanced cancer treatments.

لماذا يتم ذلك؟

Bispecific antibody therapies are mainly used to treat certain cancers, especially when other treatments — such as chemotherapy, targeted drugs or CAR-T cell therapy — have stopped working. Most bispecifics are given in specialized centers as IV infusions or as shots. Both forms are given in cycles. The study of bispecific antibodies is quickly evolving. Many of these therapies are in clinical trials.

Examples of bispecifics approved in the U.S. include:

Blood cancers and cancers of the lymphatic system

  • Blinatumomab (Blincyto) connects the immune system's T cells to leukemia cells by targeting the CD3 and CD19 proteins. It's used to treat acute lymphoblastic leukemia (ALL).
  • Teclistamab (Tecvayli) and elranatamab (Elrexfio) target CD3 and BCMA proteins to help destroy multiple myeloma cells.
  • Talquetamab (Talvey) attaches to CD3 and GPRC5D proteins to treat multiple myeloma.
  • Mosunetuzumab (Lunsumio) and epcoritamab (Epkinly) targets CD3 and CD20 to treat follicular lymphoma, a slow-growing form of non-Hodgkin lymphoma.
  • Epcoritamab (Epkinly) and glofitamab (Columvi) also target CD3 and CD20 to treat diffuse large B-cell lymphoma (DLBCL) and related lymphomas.

Solid tumors

  • Amivantamab (Rybrevant) attaches to EGFR and MET proteins to treat certain types of non-small cell lung cancer.
  • Tarlatamab (Imdelltra) links T cells to cancer cells by targeting CD3 and DLL3 proteins in small cell lung cancer.
  • Tebentafusp (Kimmtrak) connects T cells to cancer cells by binding CD3 on immune cells and the protein gp100 on tumor cells to treat uveal melanoma, a rare cancer of the eye.

Other diseases

  • Emicizumab (Hemlibra) binds factor IXa and factor X proteins to help prevent bleeding in people with hemophilia A.
  • Faricimab (Vabysmo) blocks VEGF and Ang-2, two proteins involved in leaky or diseased blood vessels, to treat macular degeneration, diabetic macular edema, and related eye diseases.

Researchers are studying bispecific antibodies for earlier stages of cancer and for other solid tumors, such as kidney and breast cancers. They're also exploring combinations of treatments, such as bispecific antibody therapy and CAR-T cell therapy, to see whether using them together or one after the other might improve outcomes.

المخاطر

Like any powerful cancer therapy, bispecific antibody therapy comes with the risk of side effects. To lower this risk, bispecific antibodies are typically given on a step-up dosing schedule. This means you get smaller doses at first. After that, the doses are increased gradually. You also may receive other medicines beforehand to help reduce the risk of side effects.

Common side effects of bispecific antibody therapy include:

Cytokine release syndrome

Bispecific antibody therapy can cause the body to release high levels of inflammatory proteins called cytokines. A sudden rise in these proteins can lead to a group of symptoms called cytokine release syndrome (CRS). This syndrome typically occurs early in treatment, often after the first few doses. Usually, CRS is mild and short-term. But in some cases, symptoms may get worse and become life-threatening.

Mild CRS can feel like you have the flu. Symptoms may include:

  • Fever.
  • Nausea.
  • Chills.
  • Low blood pressure.
  • Headache.
  • Rash.
  • Scratchy throat.
  • Difficulty breathing.
  • Racing heart rate.

Your healthcare team watches you closely after a dose. The team can identify and treat these symptoms right away.

Immune effector cell-associated neurotoxicity syndrome

Increased inflammation can sometimes affect the brain or nerves, causing a collection of symptoms known as immune effector cell-associated neurotoxicity syndrome (ICANS). Sometimes, it's just called neurotoxicity.

Usually, these changes are temporary and occur within days to weeks after a dose. Symptoms can range from mild to severe. Early treatment can help reverse these side effects. Symptoms may include:

  • Poor memory.
  • Slow reaction time.
  • Confusion.
  • Personality changes.
  • Feeling tired.
  • Loss of consciousness.
  • Numbness in your hands and feet.
  • Difficulty concentrating, talking, or breathing.

Infections

A common issue with bispecific antibody therapy is an increased risk of infections. There are a few reasons for this:

  • Fewer immune cells. While attacking cancerous cells, bispecifics also lower the number of healthy immune cells. This also can happen with other immunotherapies, such as CAR-T cell therapy.
  • Lowered helpful antibodies. Some bispecifics may lower the level of immunoglobulins in your blood. Immunoglobulins are antibodies that fight infection.
  • Lowered blood cell counts. Vigorous immune activation and resulting cytokine shifts can temporarily lower bone marrow function. This can lead to low counts of certain white blood cells.

These factors can lead to a reduced ability to fight bacterial, viral and fungal infections. Common infections after bispecific antibody therapy include:

  • Upper respiratory infections such as the common cold, flu and coronavirus disease 2019 (COVID-19).
  • Pneumonia.
  • Urinary tract infections.
  • Yeast infections.

Some infections can become serious. Your team may give you medicines to help prevent or treat infections. This may include putting antibodies directly into your blood, also called intravenous immunoglobulin (IVIg). It also may include antibiotics, antivirals and antifungals. Some are given routinely and some as needed.

Other side effects

Bispecific antibody therapy can sometimes cause allergic reactions after an infusion or injection, with symptoms such as a skin rash and trouble breathing. It also can lead to changes in liver function, causing tiredness, loss of appetite and jaundice. Other side effects may include dry skin, brittle and discolored nails, and dry mouth.

Bispecific antibody therapies may harm a fetus and are not recommended during pregnancy.

كيف تستعد؟

Talk with your healthcare team about what to expect. Factors you may want to consider ahead of time include:

  • Caregiver support. You'll need someone with you for early treatments and monitoring.
  • Time away from home. You may need to remain close to the treatment facility for the first phase of treatment. After that, you may need to travel back and forth for ongoing treatments.
  • Side effects. Occasionally, side effects of therapy can be serious.
  • High cost. Check your insurance coverage in advance.

ما يمكن أن تتوقعه

Bispecific antibody therapy is usually given at a hospital or other healthcare facility. Most people go home the same day.

Unlike some other immunotherapies, such as CAR-T cell therapy, bispecific antibody therapy isn't a one-time only treatment. It's given on a regular schedule, depending on the type of therapy you're getting and your specific needs.

Before the procedure

Before receiving a bispecific antibody medicine, your healthcare team wants you to be well hydrated. The care team may ask you to drink plenty of water. For some bispecifics, your team also may give you medicines to prevent reactions. These medicines may include steroids, antihistamines or acetaminophen.

During the procedure

The therapy can be given in two ways — as a shot or as an IV.

Bispecific antibodies that are given as a shot are placed under the skin. This leads to slower and more prolonged absorption.

Treatment typically starts with small doses that are gradually increased over days to weeks. This is called step-up dosing. After that, treatment is usually given once a week, and sometimes every two weeks after six months of good response to the treatment.

Bispecific antibody therapies that are given as an IV go directly into a vein. Putting the medicine directly into the bloodstream allows the antibodies to be absorbed quickly. They act right away against cancer cells.

The IV infusion can take up to four hours. The first infusion typically starts with smaller doses to lower the risk of side effects. Your healthcare team also gives you extra medicines, such as steroids and fluids to help prevent complications.

IV therapies are often given on day 1, day 8 and day 15 step-up schedules. After that, they are typically given every 1 to 3 weeks depending on the medicine.

Your healthcare team monitors you closely for any reactions or side effects, especially right after the first treatment. The team can provide prompt treatment as needed.

After the procedure

Most people go home the same day they receive treatment. Your healthcare team lets you know what to watch for at home. Some hospitals give you a kit to measure your temperature, blood pressure and other vital signs yourself. These measurements are sent electronically to your care team for remote monitoring. When you're home, keep track of symptoms you experience. Report any worsening or unusual symptoms to your care team right away.

Infections are common with continuing use of bispecific antibody therapies. Take these steps to reduce your risk of complications:

  • Act on symptoms. Tell your care team right away if you have signs of infection such as a fever, chills or worsening pain, especially if pain medicine does not help.
  • Get appropriate vaccines. It is important for you and those around you to stay up to date with vaccines. Ask your care team which kinds to get and when. Some vaccines use live, weakened viruses or bacteria. These may not be safe for people with weakened immune systems or those around them to get. But most common vaccines, including the flu shot, COVID-19 vaccines, RSV vaccines, pneumococcal vaccines, and the tetanus, diphtheria, pertussis (Tdap) shot are not live and are safe for people with weakened immune systems.
  • Minimize germ exposure. Taking extra measures to minimize the spread of germs can help. Preventive steps might include frequent hand-washing, limiting exposure to people who are sick, and avoiding uncooked or raw foods.

Some bispecific antibodies have unique side effects. Examples include:

  • Dry mouth.
  • Loss of sense of taste.
  • Difficulty swallowing.
  • Skin rash.
  • Brittle nails.

Tell your healthcare team if you have any other side effects, even unexpected ones. Your team might be able to help you find ways to relieve them.

النتائج

In clinical trials and real-world studies, bispecific antibody therapies have been able to help people with advanced cancer live longer. This benefit has been seen even in those who are more frail or have already received several other treatments. Bispecifics also can improve other conditions. For example, they help lower the risk of bleeding for people with hemophilia. Talk with your healthcare team about what results you might expect based on your condition and the specific therapy you are receiving.

من إعداد فريق مايو كلينك