Monoclonal antibodies (mAbs) are man-made proteins that mimic the natural antibodies produced by our immune systems. Monoclonal antibodies can be formulated into medicines to treat various types of illnesses, such as certain cancers, rheumatoid arthritis or plaque psoriasis.

These advanced treatments are useful in treating cancer. Some monoclonal antibodies are targeted treatments and attack a very specific protein (antigens) on cancer cells. Others are considered immunotherapy because they help to boost our own immune system to find and attack cancers.

What are antibodies and antigens?

We have natural antibodies in our body. Antibodies are part of our immune system and seek out foreign substances (called antigens). Antibodies respond to antigens like viruses, bacteria, cancer cell proteins or other pathogens to mount an immune response and help kill them.

• For example, our natural antibodies seek out germs (certain viruses) to kill if we have a cold or flu. Other antibodies look for antigens (proteins) on the surface of cancer cells.
• Like our natural antibodies, man-made monoclonal antibodies work similarly to help our bodies destroy substances (antigens) that can allow diseases like cancer to grow.

"Monoclonal" means that the antibody recognizes one specific antigen (protein) in the body. Some antibodies, called "polyclonal" antibodies, come from several different immune cells and recognize more than one type of antigen.

How do monoclonal antibodies work in cancer?

Monoclonal antibodies work in different ways in cancer treatment. Not all cancer cells are the same, and researchers have utilized these differences to enable specific treatments that act on those differences.

Monoclonal antibodies work by:

• Helping to identify cancer cells to be destroyed by the immune system
• Triggering an immune response to help destroy cancer cells
• Blocking cancer cell growth
• Cutting off the blood vessel growth that feeds a tumor
• Boosting the effectiveness of the immune system to kill cancer cells
• Directly attacking cancer cells
• Acting as a transport system for treatments such as radiation or chemotherapy to deliver treatment directly to the cancer cells
• Using two monoclonal antibodies to help the immune system cells identify and attach to cancer cells (bispecific products)

For example, targeted therapy works by interacting with specific targets (instead of affecting all cells) found in cancer. Immunotherapy treatments help to boost our own immune system to work better against cancers found in the body. Immune checkpoint inhibitors, like Keytruda (pembrolizumab) or Opdivo (nivolumab) are examples of this type of mAb.

Monoclonal antibody-based treatments are now considered a standard part of cancer therapy when needed, alongside other options, such as surgery, chemotherapy, hormone treatment or radiation therapy.

What types of monoclonal antibodies are there?

Monoclonal antibodies (mAbs) may be classified as either Naked, Conjugated or Bispecific. They are usually made in the lab from mouse proteins, human proteins or a combination of the two.

Naked mAbs: The types of treatments are usually given alone and usually attach to antigens on cancer cells, but may attach to healthy cells or other proteins. They have no other components, like radioactive materials or medicines, attached to them.

• These are the most common type of monoclonal antibody used clinically.
• One example of naked mAb is Herceptin (trastuzumab) which targets the HER2 protein in breast or stomach cancers. HER2 can help cancer cells to grow

Conjugated mAbs: These agents are combined with chemotherapy or radioactive treatments. These tagged or labeled mABs help direct the treatment specifically to the cancer cells.

• One example is Zevalin (ibritumomab tiuxetan), a radioimmunotherapy. It binds specifically to the CD20 antigen which is found on white blood cells called B cells. It is used to treat non-Hodgkin's lymphoma (NHL). The mAb (ibritumomab) delivers a radioactive substance (Yttrium-90) directly to cancer cells.
• Another example is Kadcyla, an mAb that is attached to a chemotherapy drug. It targets the HER2 protein and is used to treat HER2-positive, metastatic breast cancer.

Bispecific mAbs: These medicines contain 2 mAbs which allow them to attach to 2 different proteins.

• One example is Lunsumio (mosunetuzumab-axgb, used to relapsed or refractory (R/R) follicular lymphoma, a type of blood cancer that affects white blood cells.
• It targets the CD20 antigen on the surface of B cells (cancerous white blood cells) and CD3 on the surface of T cells (a white blood cell that helps to protect you from disease.). The mAb redirects the existing T cells to target B cells by releasing cytotoxic proteins into the B cells to kill the cancer.

What diseases do monoclonal antibodies treat?

Some of the diseases that can be treated with monoclonal antibodies include:

• Cancer like blood cancers and solid tumors
• Inflammatory bowel disease, like Crohn’s disease or ulcerative colitis
• Severe allergies
• Autoimmune disorders
• Infections
• Osteoporosis
• Severe asthma
• Eye conditions, like thyroid eye disease (TED)
• Migraine headaches
• High cholesterol
• Alzheimer’s disease

Active research is ongoing to develop new medicines and find new uses for monoclonal antibodies. You may be eligible to join a clinical trial for treatment. Speak to your doctor about this option.

What are some examples of monoclonal antibodies?

Orthoclone OKT3 (muromonab-CD3) was the first licensed monoclonal antibody in the U.S. It gained clearance from the FDA in 1986 for use in preventing kidney transplant rejection.

List of monoclonal antibodies and diseases they treat:*

• Aduhelm (aducanumab) - Alzheimer's disease
• Avastin (bevacizumab) - brain tumors, and cancers of the kidney, liver, lung, colon, rectum, cervix, ovary, or Fallopian tube
• Blincyto (blinatumomab) - Acute lymphoblastic leukemia
• Cosentyx (secukinumab) - plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, enthesitis-related arthritis, and non-radiographic axial spondyloarthritis
• Fasenra (benralizumab) - severe asthma
• Humira (adalimumab) - rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, Crohn's disease, and ulcerative colitis (among others).
• Herceptin (trastuzumab) - breast cancer, advanced gastric (stomach) cancer
• Kesimpta (ofatumumab) - relapsing multiple sclerosis (MS)
• Keytruda (pembrolizumab) - liver, skin (melanoma), lung, breast or esophageal cancer (among others)
• Ocrevus (ocrelizumab) - multiple sclerosis
• Opdivo (nivolumab) - melanoma (advanced skin cancer), non-small cell lung cancer, renal cell (kidney) cancer, bladder cancer (among others)
• Remicade (infliximab) - rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, ulcerative colitis and Crohn's disease
• Rituxan (rituximab) - non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (among others)
• Skyrizi (risankizumab) - plaque psoriasis, psoriatic arthritis, Crohn’s disease
• Takhzyro (lanadelumab-flyo) - prevention of attacks of hereditary angioedema (HAE)
• Taltz (ixekizumab) - plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis
• Tepezza (teprotumumab) - thyroid eye disease (TED or Graves Eye Disease)
• Tremfya (guselkumab) - plaque psoriasis, psoriatic arthritis
• Xolair (omalizumab) - allergic asthma, nasal polyps and chronic hives (chronic spontaneous urticaria).

More recent monoclonal antibodies approved by the FDA include:

• Columvi (glofitamab) - diffuse large B-cell lymphoma
• Elahere (mirvetuximab soravtansine-gynx) - ovarian cancer
• Epkinly (epcoritamab-bysp) - diffuse large B-cell lymphoma (DLBCL)
• Leqembi (lecanemab-irmb) - Alzheimer’s disease
• Lunsumio (mosunetuzumab-axgb_- follicular lymphoma
• Zynyz (retifanlimab-dlwr) - Merkel cell carcinoma (an aggressive type of skin cancer)

New monoclonal antibodies are constantly under research. For example, toripalimab is an investigational monoclonal antibody treatment for nasopharyngeal carcinoma, a rare type of head and neck cancer, but is not yet approved by the FDA for this use. If approved, it would be the first PD-1 immunotherapy agent cleared for advanced nasopharyngeal carcinoma.

• Loqtorzi (toripalimab)

Learn more: What is the mechanism of action (MOA) of Loqtorzi (toripalimab)?

^{*Note: This is not a complete list of all monoclonal antibodies available on the U.S. market or their indications. New drugs and uses are frequently approved by the FDA. If you have further questions about monoclonal antibodies you can search by name here or contact your healthcare provider.}

How are monoclonal antibodies given?

These medicines are often injected into a vein (intravenously). You may receive this treatment at a special clinic called an infusion center. Your doctor will monitor you for any infusion or allergic reactions before you go home.

In some cases, monoclonal antibodies are injected subcutaneously (just under the skin) instead of into a vein.

Different drugs will have different schedules for administration based on your cancer type. Not all cancer regimens include monoclonal antibodies as part of the treatment plan.

Are biosimilars approved for monoclonal antibodies?

Biosimilars are increasingly being approved for many biologics, including monoclonal antibodies.

• A biosimilar is a biological product that is similar to the reference product (usually the original brand name product).
• Biosimilars have no clinically meaningful differences in terms of safety, purity, and potency.
• Unlike most chemically-derived small-molecule drugs, biological products are generally derived from a living organism, such as microorganisms or yeast.

A biosimilar is not considered a “generic” in the same way that a traditional, small molecule drug (for example: ibuprofen or acetaminophen) is classified as a generic. As with generics, biosimilar cost savings for healthcare systems and the consumer are expected to be significant.

One example is Amjevita (adalimumab-atto), a a tumor necrosis factor blocker and the first biosimilar approved for Humira. It is used for most of the same indications as Humira, including rheumatoid arthritis, Crohn's disease and psoriasis, but is not approved for uveitis. In this case, Humira is the reference product.

Learn more: What biosimilars have been approved in the United States?

What side effects occur with monoclonal antibodies?

A wide range of side effects can occur with monoclonal antibodies, depending upon your drug treatment and use. Some side effects can be very rare but can be serious or life-threatening, while other side effects may be common but not serious.

Talk with your healthcare provider about which side effects to expect from your treatment.

Common side effects

In general, common side effects with monoclonal antibodies can include:

• Allergic reactions, such as hives or itching
• Flu-like symptoms (chills, extreme tiredness, fever, and muscle aches and pains)
• Nausea and vomiting
• Diarrhea
• Skin rashes
• Low blood pressure

Infusion reactions, which are more common when the drug is first being started, can include low blood pressure, fever, chills, skin rash, weakness, nausea/vomiting, headache, or diarrhea. Your doctor may give you medicine before your treatment to help prevent this side effect. Your cancer care team will watch you closely for this side effect.

Serious side effects

Serious, but less common, side effects may include:

• Serious infusion reactions, which can be a life-threatening allergic reaction.
• Heart problems like a risk for high blood pressure, congestive heart failure and heart attacks.
• Lung inflammation or other lung problems.
• Skin problems, like sores and rashes or sores on the tissue that lines your cheeks and gums (mucosa).
• Increased risk of serious bleeding, like internal bleeding.

To learn more about clinical trails through the National Cancer Institute, visit here.

This is not all the information you need to know about Monoclonal Antibodies for safe and effective use and does not take the place of your doctor’s directions. Review the full product information you receive about your medicine. Discuss this information and any questions you have with your doctor or other health care provider.