How Bispecific Antibodies Are Changing Diffuse Large B-Cell Lymphoma Treatment

Describing this new immunotherapy, Dr. Lulla explains, “Think of this as CAR T-Cells, except they give you a molecule off the shelf, without actually having to engineer anything from your own cells. It brings the cancer and T cells together and still has an immunotherapy effect.”

This “off-the-shelf” nature is important. Unlike CAR T-Cell Therapy, which requires removing your own immune cells, modifying them in a lab, and reinfusing them weeks later, bispecific antibodies are ready-made medications that can be administered more quickly and easily.

While classical immunotherapy binds to a single target on a T-Cell or a cancer cell to stimulate the immune system, bispecific antibodies bring cancer cells and your body’s immune cells, called T-Cells, in proximity to one another, allowing your body’s immune system to recognize and eliminate your cancer.

Here we will discuss the risks and benefits of this new therapy:

How This New Treatment Targets Cancer

Antibodies are natural proteins made by the immune system to recognize and attack things that don’t belong in your body — such as bacteria, viruses, or cancer cells. Each antibody has a unique “Y” shape that allows it to attach to a specific target, like a key fitting perfectly into a lock.

Most standard antibodies used in medicine bind to one target. Bispecific antibodies, however, are designed to connect to two different targets at the same time — one on the cancer cell and one on an immune cell, usually a T cell, which is a powerful type of white blood cell responsible for killing abnormal cells.

By binding to both, bispecific antibodies act like a bridge — bringing the cancer cell and the T-Cell into close contact. This proximity “shows” the immune system where the cancer is hiding, allowing the T-Cell to recognize, attack, and destroy the cancer cell.

WATCH: How Do Biospecific Antibodies Work?

Which Patients May Benefit from Bispecific Antibodies?

These therapies are often used in people whose cancer has come back (relapsed) or stopped responding (refractory) to previous treatments such as chemotherapy, stem cell transplant, or CAR T-Cell Therapy.

Because bispecifics are relatively new, doctors carefully evaluate whether each patient is a good candidate. Factors such as your overall health, the type and stage of your cancer, prior treatments, and how well your body can tolerate immune activation all play a role.

Clinical trials are also exploring the use of bispecific antibodies earlier in treatment, and even in solid tumors such as lung or prostate cancer. As research continues, the hope is to expand their use to more patients and cancer types.

How Is the Drug Delivered?

Bispecific antibodies are typically given as an intravenous (IV) infusion — meaning they are administered through a vein, similar to how chemotherapy is given. Some newer bispecifics can also be delivered subcutaneously, as an injection under the skin.

Treatment is usually given in a hospital or infusion center under close supervision, especially for the first few doses. This allows the care team to monitor for side effects and intervene quickly if needed.

Depending on the specific drug, infusions may occur weekly at first, then be spaced out over time as your body adjusts and responds. Some patients continue treatment for several months, while others may stay on therapy longer if they’re responding well.

What Are the Potential Benefits?

The greatest benefit of bispecific antibody therapy is that it gives patients another treatment option when other approaches have stopped working. For some people, these drugs have produced deep and lasting remissions, even after multiple prior therapies.

Other advantages include:

• No need for cell collection or genetic modification (unlike CAR T therapy)
• Faster time to treatment, since it’s “off the shelf”
• Potential for outpatient administration after the initial doses
• Targeted immune activation, which focuses the immune system’s attack on cancer cells rather than healthy tissues

For many patients, bispecific antibodies represent hope and flexibility — a way to continue fighting their disease while maintaining quality of life.

What Are the Possible Side Effects?

Because bispecific antibodies activate the immune system, they can cause immune-related side effects. Some of these are similar to those seen with other immunotherapies.

The most common is cytokine release syndrome (CRS) — a temporary reaction caused by the rapid activation of immune cells. Symptoms may include fever, chills, fatigue, low blood pressure, or shortness of breath. Most cases are mild to moderate and occur within the first few doses. Doctors can manage CRS effectively with medications such as tocilizumab (Actemra) or steroids and careful monitoring.

WATCH: Assessing the Impact of Cytokine Release Syndrome

Another possible side effect is neurologic toxicity (sometimes called ICANS), which can cause confusion, tremors, or difficulty speaking. This is less common but also reversible when treated promptly.

Other typical side effects may include:

• Fatigue
• Low blood counts
• Infections
• Injection site reactions (for subcutaneous formulations)

Your healthcare team will watch for these reactions closely and adjust your treatment plan if needed. Most patients can continue therapy safely with proper monitoring and supportive care.

Other Disadvantages

Currently, bispecific antibodies are considered a third-line treatment for patients with relapsed/refractory lymphomas. It requires multiple infusion sessions and may lead to exhaustion of the T-cells, meaning they will no longer respond to therapy.

Balancing Risks and Benefits

Every treatment has risks and benefits, and bispecific antibody therapy is no different. The key is finding the right balance for each individual. For many patients, especially those with limited remaining options, the potential benefits of tumor control or remission outweigh the risks of manageable side effects.

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