Bispecific monoclonal antibody therapy is a new class of drug that is emerging with several new treatments currently being investigated. This class of drug is also known as a T-cell engaging bispecific monoclonal antibody.
What is a bispecific monoclonal antibody?
The production of antibodies is a major function of the immune system and is carried out by a type of white blood cell called a B-cell (B lymphocyte). Antibodies can be triggered by and directed at foreign proteins, bacteria or viruses or toxins, that are also known as antigens.
Scientists have developed antibody treatments that are made in the laboratory. These antibody treatments are designed to target specific proteins that are on the surface of certain malignant B-cells. The first type of treatment that was created is called a monoclonal antibody therapy. The first therapy created is called rituximab. These bind to one specific protein on the surface of certain B-cells.
A bispecific monoclonal antibody is an antibody that can bind to two different antigens at the same time. They are also known as a T-cell engaging bispecific antibody that binds to an antigen on the surface of a T-cell and to the surface of a B-cell at the same time.
This treatment is like other T-cell engaging therapies such as CAR T-cell therapy. This drug is manufactured in the laboratory and it offers off-the-shelf availability of a drug. This is much quicker than collecting a patient’s T-cells to re-engineer in the laboratory before giving them back to the patient. Both methods engage T-cells to then recognise and kill malignant (cancerous) B-cells.
Mosunetuzumab
Mosunetuzumab is currently under investigation and is only available in a clinical trial.
Mosunetuzumab is a humanised T-cell engaging bispecific monoclonal antibody. A bispecific monoclonal antibody is an artificial protein that can simultaneously bind to two different types of antigens. It simultaneously binds to CD3 and CD20. CD3 is a protein found on the surface of T-cells and CD20 is a protein found on the surface of B-cells.
It works by redirecting T-cells to engage and eliminate the malignant B-cells. They eliminate target B-cells by releasing cytotoxic proteins into the B-cells.
What are the indications of use?
This therapy is currently under investigation in several trials. Mosunetuzumab has demonstrated durable (lasting) complete responses in people with relapsed or refractory non-Hodgkin lymphoma (NHL).
How is it given?
- Mosunetuzumab is given either through a drip (intravenous infusion) or as an injection just underneath your skin (subcutaneous injection)
- The treatment is given every 21 days
- It is given up to 17 cycles of treatment
Possible side effects
Notable side effects include cytokine release syndrome (CRS) in 29% and neurological adverse events occurred in 4% percent of patients.
CRS is an acute systemic inflammatory syndrome. The common side effects of this include high fever, fatigue, nausea, and multiple organ dysfunction.
Glofitamab (CD20-TCB)
Glofitamab is currently under investigation and is only available in a clinical trial.
CD20-TCB has recently been named ‘Glofitamab’. Glofitamab is a new type of T-cell engaging bispecific monoclonal antibody. This new therapy is currently not approved for commercial use and is only available in clinical trials.
A bispecific antibody is an artificial protein that can combine to two different types of antigens (a foreign substance or toxin) at the same time, to start an immune response in the body. Bispecific antibodies are different to the original monoclonal antibodies that bind to only one type of antigen (these include rituximab and Obinutuzumab).
The advantage of these new generation antibodies is that they can have more cytotoxic (cell death) effects on lymphoma cells.
How does this drug work?
Glofitamab binds to the target CD20 antigen on the surface of the malignant B-cell and CD3 antigen on the surface of T-cells at the same time. The binding to these antigens activates (or engages) and redirects a patient’s existing T-cells. These T-cells then engage and eliminate the malignant B-cells by releasing cytotoxic proteins into the B-cells to kill them.
This treatment is like other T-cell engaging therapies such as CAR T-cell therapy, however it offers off-the-shelf availability and less time for treatment to be given. This novel therapy has so far shown high response rates, durable remissions and is well tolerated by patients, for a patient group that has a poor prognosis.
What are the indications of use?
Glofitamab is currently being investigated for patients with relapsed or refractory non-Hodgkin lymphoma (NHL).
How is it given?
Patients are given Obinutuzumab (a monoclonal antibody) once a week prior receiving Glofitamab. This is to reduce the amount of lymphoma cells present to reduce side effects.
Possible side effects
The most common side effect was consistent with other T-cell engaging treatment reported as cytokine release syndrome (CRS). This generally only occurred after cycle 1 and symptoms were manageable.
CRS is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction. Close monitoring is needed.
Further information
Glofitamab is currently only available in clinical trials, including in Australia.
For more information you can find out more about Glofitamab and what are bispecific antibodies from our recent interview with Dr Michael Dickinson, Peter MacCallum Cancer Centre & Royal Melbourne Hospital:
