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?
Antibodies are naturally made in our body by our mature B-cell lymphocytes (also called plasma cells). They are special proteins that bind to germs and damaged or diseased cells to help your immune system destroy cells that could be harmful to you.
However, antibodies can also be grown in a laboratory and made with extra features. A bispecific monoclonal antibody is made in the laboratory and has an extra feature. While naturally occurring antibodies are only able to bind to one cell receptor – which is a very specific receptor on a specific cell; Bispecific monoclonal antibodies are made to bind to specific receptors on two different cells.
The bispecific antibody is able to attach to a receptor on your T-cell lymphocyte which is a specialised immune cell effective at fighting infection and disease. The antibody then takes the T-cell to the cancerous lymphoma cell and attaches to a receptor on the lymphoma cell. This way the bispecific antibody delivers the T-cell to the lymphoma so it can fight the lymphoma more effectively.
Because the bispecific antibody helps the T-cell work more effectively by taking it to the lymphoma cell, they are called T-cell engaging therapy.
Â
Some bispecific monoclonal antibodies target the same receptors that CAR T-cell therapies target (such as CD19 on your lymphoma cell and CD3 on your T-cell). However bispecific antibodies do not use your own T-cells, so can be ordered and given to you more quickly and may cost less.
However, these medications are new and currently only approved for use in clinical trials in Australia.
Â
Mosunetuzumab
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 some 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)
In rare cases, your haematologist may be able to get access to glofitamab in other ways, but you will probably have to pay for it. This would not be suitable for everyone, and rules around this are different in every state. Speak to your haematologist if you would like to know if this is an option for you.
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:
