The immune system is responsible for protecting the body from foreign substances.[1] Immunotherapy is a treatment that utilizes the body’s immune system to attack and kill cancer cells. Monoclonal antibodies (mAbs) are a type of immunotherapy, but they can also act as targeted therapies depending on the type of antigen targeted.[2] mAbs are man-made versions of antibodies, immune system proteins that can identify foreign substances (antigens) and trigger an immune reaction to kill them. mAbs can be made from proteins found in mice only (murine), proteins found in humans only (human), a combination of part mouse protein and part human protein (chimeric), or small parts of mouse proteins attached to human proteins (humanized).[3]

The three main types of monoclonal antibodies used to treat cancer are naked mAbs, conjugated mAbs, and bispecific mAbs. Naked mAbs, the most common type of mAbs used to treat cancer, have nothing attached to them. They typically bind to antigens on cancer cells, but some work by binding to noncancerous cells or free-floating proteins. When naked mAbs bind to cancer cells, they act as a marker so the immune system can attack the cancer. Some naked mAbs target immune system checkpoints. These checkpoints are in place to regulate the immune system, so blocking these checkpoints boosts the immune system.[3]

Naked mAbs that bind to other cells to block antigens that fuel tumor growth function as targeted therapies. For example, the HER2-targeted drug trastuzumab (brand name: Herceptin) is a monoclonal antibody that attaches to HER2 (human epidermal growth factor receptor 2) on tumors.[3] HER2, a protein encoded by the HER2 gene, promotes growth; therefore, breast cancers with an excess of this protein tend to grow and spread quickly.[4] By binding to the HER2 protein, the monoclonal antibody slows or halts the growth of the cancer cells.[3]

Conjugated mAbs (also known as tagged antibodies, labeled antibodies, or loaded antibodies) are attached to a chemotherapy drug (chemolabeled antibody) or a radioactive substance (radiolabeled antibody). The antibody is able to deliver the chemotherapy or radiation directly to the cancer cells when it binds to them. This technique leads to less side effects than traditional chemotherapy or radiation because normal cells in other parts of the body are not affected. Bispecific mAbs contain parts of two different mAbs, allowing them to attach to two different antigens at the same time. These antibodies can be used to bring immune cells and cancer cells together by binding to both.[3]

mAbs are administered intravenously (by IV). The most common side effects of mAbs are fever, chills, rash, nausea, vomiting, diarrhea, weakness, headache, and low blood pressure. Allergic reactions also may occur. Naked mAbs tend to have less side effects than chemotherapy. Side effects relating to the specific antigen that is targeted are also possible.[3]

References

1.     Immune System https://my.clevelandclinic.org/health/articles/21196-immune-system (accessed Jun 16, 2021).

2.     Immunotherapy https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy.html (accessed Jun 16, 2021).

3.     Monoclonal Antibodies and Their Side Effects https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/monoclonal-antibodies.html (accessed Jun 16, 2021).

4.     Types of Breast Cancer: Triple Negative, ER-Positive, HER2-Positive https://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-positive (accessed Apr 30, 2021).