What is Bispecific T-Cell Engager (BiTE) Therapy?

Bispecific T-cell engager (BiTE) therapy is a groundbreaking immunotherapy that enables the body’s own immune system to target tumor cells with unprecedented precision. Unlike traditional cancer immunotherapies—which rely solely on the ability of the immune system to identify and destroy cancer cells—BiTE therapy takes this novel approach one step further. By establishing a direct connection between immune cells (T cells) and cancer cells, BiTE therapy can amplify the body’s specific immune response to cancer.

In research studies performed to date, BiTE therapy has shown significant promise in improving cancer outcomes, particularly for hematologic cancers. These results highlight the potential of BiTE therapy for other cancers with similar mechanisms as well as certain solid tumors that are resistant to other treatments. Notably, BiTE therapy is often associated with milder side effects compared to conventional therapies.

What are bispecific antibodies and how are they used in BiTE therapy?

Engineered in a laboratory, bispecific antibodies (BsAbs) are designed to bind to two different targets simultaneously. BiTE therapy uses a specialized class of BsAbs that has one binding site for a specific antigen found on a cancer cell and another for a receptor on a T cell (usually CD3). This unique structure allows the antibodies to create a direct bridge between the T cells and the cancer cells. By forging this connection, BiTE therapy streamlines the pathway for attack and destruction, enhancing the effects of cancer treatment.

What is the difference between chimeric antigen receptor (CAR)-T cell therapy and bispecific T-cell engager therapy?

CAR-T cell therapy and BiTE therapy are both immunotherapies that harness the power of T cells to fight cancer, but they work in distinct ways. CAR-T cell therapy involves collecting a patient’s T cells and genetically modifying them in a lab to express specific CARs that can recognize cancer cells. The modified T cells are then infused into the patient. The CARs provide the T cells with a direct ability to bind to and destroy cancer cells that carry the target antigen. CAR-T cell therapy is personalized, meaning each patient’s T cells are specifically engineered for their treatment.

Bispecific T-cell engager therapy, on the other hand, uses engineered antibodies that have two binding sites—one for a target on cancer cells and the other for a target on T cells. This dual binding capability brings T cells directly into contact with cancer cells, helping to activate the T cells and initiate an immune response against the cancer cells. Unlike CAR-T cell therapy, BiTE therapy does not involve modifying a patient’s T cells. Instead, it utilizes “off-the-shelf” BsAbs that begin to work immediately upon injection.

In sum, CAR-T cell therapy customizes a patient’s own T cells through genetic modification, while BiTE therapy uses BsAbs to activate a patient’s T cells against cancer cells without modifying them. Both approaches aim to connect T cells with cancer cells, but CAR-T cell therapy is personalized and requires cell modification, while BiTE therapy is universal and ready to use.

What types of cancers can be treated with bispecific T-cell engager therapy?

Thus far, BiTE therapy has shown promise for several types of cancer, including:

• Acute lymphoblastic leukemia (ALL) – Blinatumomab (Blincyto) is a BiTE that targets CD19 on B cells and is approved for treating certain forms of ALL. Blincyto connects T cells with B-cell leukemia cells, activating an immune response against the cancer.
• Non-Hodgkin lymphoma (NHL) – Research on BiTEs targeting CD20 or CD19, markers common on B cells, has shown potential in treating various types of B-cell NHL.
• Multiple myeloma – Certain BsABs are currently being explored in clinical trials to target the B-cell maturation antigen (BCMA) found on multiple myeloma cells. This includes BiTEs designed to bring T cells into proximity with BCMA-expressing cancer cells.
• Other blood cancers – BiTEs targeting various surface markers are being developed and tested for other hematologic malignancies, such as chronic lymphocytic leukemia (CLL) and myeloid leukemias.
• Solid tumors – While still largely in the experimental phase, BiTEs targeting antigens such as human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and prostate-specific membrane antigen (PSMA) are under investigation for solid tumors, such as breast cancer, lung cancer, prostate cancer and gastric cancers. Although targeting solid tumors with immunotherapy poses unique challenges, early research is promising.

BiTE therapy’s adaptability and ability to target specific markers offer potential for broader applications across various types of cancers in the future.

What are the side effects of bispecific T-cell engager therapy for cancer?

Like other immunotherapies, BiTE therapy may cause side effects, which can vary in severity depending on the type of cancer, the specific BiTE used and the patient's response to treatment. Possible side effects include:

• Cytokine release syndrome (CRS) – A potentially serious side effect of BiTE therapy, CRS occurs when T cells release a large number of immune system-stimulating proteins (cytokines) into the bloodstream, triggering an overly robust immune response. Symptoms can include fever, nausea, headache, rash, rapid heartbeat, low blood pressure and difficulty breathing.
• Neurological symptoms – Some patients experience headaches, confusion, dizziness, seizures and difficulty speaking or understanding language (aphasia).
• Hematologic toxicity – Low blood counts, particularly of white blood cells (neutropenia) and platelets (thrombocytopenia), may increase the risk of bleeding and infection.
• Gastrointestinal symptoms – During BiTE therapy, many patients experience mild nausea, vomiting, diarrhea and loss of appetite, which can impact comfort and quality of life.
• Fatigue – Many patients report significant fatigue when receiving immunotherapy, which can linger even after treatment ends.
• Recurrent infections – BiTE therapy can increase the risk of infection, particularly if blood counts are low.

Often, these side effects can be managed with supportive treatments, such as corticosteroids and other immunosuppressive drugs, which can help alleviate the symptoms of CRS and other inflammatory responses. Regular monitoring and early intervention are critical to effective side effect management.

Moffitt's SONIC (Specialized Oncology Non-Cellular Immunotherapy Comprehensive Care) program provides specialized care during the first two cycles of bispecific antibody treatment, when side effects are most prevalent. Patients receive specialized care from a multispecialty team, including an infectious disease team to manage potential complications, along with physicians, advanced practice providers, nurses and pharmacists trained to identify and manage side effects and adverse events associated with bispecific antibody treatments.

How is bispecific T-cell engager therapy evolving?

BiTE therapy is rapidly progressing, with advancements focused on improving its precision, reducing its side effects, and expanding its use across different cancer types. Key developments include:

• Target expansion – Researchers are developing BiTEs to target more specific markers found on a broader array of tumors, making the therapy applicable to more cancer types beyond hematologic cancers. This includes ongoing trials for solid tumors, which have historically been challenging to treat with BiTEs due to their complex cellular microenvironments.
• Reduced toxicity – New generations of BiTEs are being engineered to reduce the risk of severe side effects, particularly CRS and neurotoxicity. By refining targeting precision and controlling the activation strength of T cells, researchers aim to make BiTE therapy safer and better tolerated.
• Improved stability and delivery – Advances in drug design are making BiTEs more stable in the bloodstream, which allows for longer-lasting effects and the potential for less frequent dosing. This development could improve patient comfort and adherence while maintaining therapeutic efficacy.
• Combination therapies – BiTE therapy is increasingly being tested in combination with other treatments, such as immune checkpoint inhibitors, to enhance its efficacy. Combining BiTEs with other immunotherapies may create synergistic effects, helping the immune system recognize and attack tumors more effectively.
• Optimized formats – Tri-specific antibodies, which target two tumor antigens and the T cell receptor simultaneously, are being explored to further refine BiTE therapy’s targeting capabilities. This can enhance its potency by making it more difficult for cancer cells to evade treatment.

These and other advancements in BiTE therapy represent promising steps toward making it a more flexible, effective and patient-friendly option within the broader field of cancer immunotherapy.

Is bispecific T-cell engager therapy approved by the U.S. Food and Drug Administration?

The FDA granted accelerated approval of BiTE therapy for certain types of cancer, marking a significant milestone in treatment and providing many patients with additional options. One example is tarlatamab-dlle (Imdelltra) for treating late-stage small cell lung cancer (SCLC) that has advanced after platinum-based chemotherapy. By binding to both tumor cells and T cells, Imdelltra helps the immune system precisely target the DLL3 protein that is overexpressed in SCLC cells. This dual-binding effect activates the T cells to attack the cancer cells more effectively. In clinical trials, Imdelltra has shown a 40% objective response rate, with some patients experiencing an extended clinical benefit.

Bispecific T-cell engager therapy at Moffitt Cancer Center

If you would like to learn more about BiTE therapy, you can request an appointment with a specialist at Moffitt by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.