Bispecific Antibodies

October 24, 2024

This page was reviewed under our medical and editorial policy by Alexis Boling, MSN-RN, CNML, director, nursing, Immune Effector Cell & Gene Therapy Program, City of Hope^® Cancer Center Duarte

Bispecific antibodies (bsAbs) are a type of monoclonal antibody used in immunotherapy. They are created in a laboratory and are made from parts of two different monoclonal antibodies.

Monoclonal antibodies were first approved in the United States in 1986; since then, they have become important tools in the fight against cancer. Bispecific antibodies were developed with the dual aim of helping patients overcome tumor drug resistance and making antibody-based treatment more successful.

What Is a Bispecific Antibody?

A bispecific antibody is a laboratory-made antibody that has two halves, or two binding areas, that allow it to attach to other cells in the body.

The immune system protects the body by making antibodies, key proteins that circulate in the blood and stick to specific antigens on germs or other foreign substances. Once attached, antibodies help other parts of the immune system destroy these invaders.

Researchers may create antibodies that target specific antigens, like those found on cancer cells. These lab-made antibodies, called monoclonal antibodies, are used to treat various diseases, including cancer. But identifying the appropriate antigens on cancer cells is challenging, and monoclonal antibodies are more successful against some cancers than others. That’s where bispecific antibodies come in.

Bispecific antibodies combine parts of two different monoclonal antibodies into one drug. This allows them to attach to two different proteins at once — on the cancer cell and on another immune system cell — and attract them to each other. They offer a promising approach by helping the immune system recognize and target cancer cells, boosting the body’s natural ability to fight cancer.

How Do Bispecific Antibodies Work?

Bispecific antibodies are lab-created proteins given intravenously that mimic the body’s natural antibodies. Unlike regular antibodies, which only bind to a single antigen, bispecific antibodies attach to two different antigens simultaneously.

For example, some bsAb drugs are designed with one part that attaches to a protein on cancer cells and another part that binds to a protein immune system fighter cell called a T cell. This connection helps bring the T cells into contact with the cancer cells. This process may enable the immune system to mount a more successful response against the cancer, unlocking the door for the immune system to detect and destroy cancer cells.

Which Cancers Do Bispecific Antibodies Treat?

Since bispecific antibodies were discovered, researchers have studied hundreds of similar compounds, seeking new or more appropriate options for treating cancer. Following are some bispecific antibodies that are currently approved by the U.S. Food and Drug Administration to treat cancer.

Blinatumomab (Blincyto^®) is approved to treat certain types of acute lymphocytic leukemia.

Amivantamab (Rybrevant^®) is approved to treat some non-small cell lung cancers that have spread.

Teclistamab (Tecvayli^®) may treat multiple myeloma that has not responded to treatment or has come back.

Mosunetuzumab (Lunsumio^™) may treat follicular lymphoma that has not responded to treatment or has come back.

Epcoritamab (Epkinly^™) and glofitamab (Columvi^™) are both approved for diffuse large B cell lymphoma that has not responded to treatment or has come back.

Talquetamab (Talvey^®) and elranatamab (Elrexfio^™) are both approved for multiple myeloma that has not responded to treatment or has come back.

Tebentafusp (Kimmtrak^®) is approved for treating patients with certain types of uveal melanoma that have returned or are unable to be treated surgically.

Cadonilimab may treat cervical cancer that has spread or come back after treatment.

Types of Bispecific Antibodies

Bispecific antibodies come in different types and shapes. These differences help determine how they work in the body, the conditions they may help treat and other properties such as how long they survive in the body. The two main categories of bispecific antibodies are IgG-based bsAbs and fragment-based bsAbs.

IgG-based bispecific antibodies: IgG-based bsAbs are similar in structure to those made by the body and resemble a Y shape. A special area on the tail of the Y helps the antibody perform various functions, such as destroying cancer cells. It also helps them live longer in the body. But IgG-based bispecific antibodies may sometimes cause side effects due to binding to the wrong target. Their intricate structure also makes them challenging to make in the lab.

Fragment-based bispecific antibodies: Fragment-based bsAbs are smaller and less complex dual-antibodies, allowing them to be more nimble and penetrate tissue with greater ease. Their simplicity makes them easier to produce in the lab. However, they lack the special tail found on IgG-based antibodies, making their survival in the body shorter (though researchers are working to enhance this). One of the most well studied of these is blinatumomab, a bispecific T cell engager (BiTE). In BiTEs, one part of the drug attaches to a T cell and the other sticks to a protein on a cancer cell. This makes it easier for the immune system to destroy the cancer cells.

Bispecific Antibodies at City of Hope

Researchers at City of Hope are at the forefront of research and innovations involving bispecific antibodies. Our scientists are constantly evaluating new options and improving the efficacy of existing bispecific antibody therapies to develop more powerful cancer treatments.

Learn more about our bispecific antibodies research