There are many different types of targeted therapies that work in different ways. On this page we will describe what they are, how they work and some of the common targeted therapies that are currently being used or being investigated in clinical trials.
What are targeted therapies?
Targeted therapy is a type of cancer treatment that targets your own specific type and stage of cancer. Targeted therapies concentrate on the difference between healthy cells and cancer cells and interfere with the specific molecules in the cancer cells that tell them to grow and spread.
By attacking these molecules and the specific changes in the cancer cell, targeted therapies can block the abnormal progression of those cells causing the cancer.
The aim of targeted therapy is to only target and attack cancer cells
Who can have targeted therapies?
- Patients who have been treated before but need more treatment because their lymphoma has relapsed (come back)
- Patients who did not respond well to their previous treatment (refractory lymphoma)
- Patients who cannot have other standard treatments.
What types of targeted therapies are used in lymphoma?
There are many different types of targeted therapies that are used in the treatment of lymphoma. It is a quickly growing and changing area, as scientists understand more about how lymphoma develops in the microenvironment of the cancer cell. Below we will discuss the following main types of targeted therapies that include:
- Antibody therapy
- Checkpoint inhibitors
- CAR T-cell therapy
- Cell signal blockers
- Programmed cell death inducers
- HDAC inhibitors
- Cytokine therapy
These types of therapies are technically targeted immunotherapies as well, but we will discuss them on a separate page. On this page we will discuss further:
- Monoclonal antibody therapy
- Antibody drug conjugates (ADC)
- Bispecific monoclonal antibodies
Checkpoint inhibitors are medicines that block the signalling through immune checkpoints in a cell. Lymphoma can avoid detection by your immune system. Checkpoint inhibitors allow these checkpoints to be turned on and so the lymphoma can be detected.
These checkpoints are a normal part of the immune system and keep immune responses from being too strong. By blocking them, these drugs allow your immune cells to respond more strongly to cancer.
Our immune system’s T-cells have proteins on them that turn on an immune response and other proteins that turn it off. These are called checkpoints. Cancer cells sometimes find ways to use these checkpoints to hide from the immune system. They do this by making high levels of proteins to switch off T-cells when the T-cells should really be attacking the cancer cells.
Checkpoint inhibitors work by blocking the proteins that stop the immune system from killing cancer cells. When checkpoint inhibitors block these proteins, this turns the immune system back on and the T-cells can find and destroy the cancer cells. There are many different types of checkpoint inhibitors. Whether you have this treatment depends on what treatment you have had to date and the stage of your cancer.
Checkpoint inhibitors showing promise for lymphoma include:
- Pembrolizumab (Keytruda)
- Nivolumab (OPDIVO)
Chimeric antigen receptor (CAR) T-cell therapy
Your immune system has T-cell lymphocytes, a type of white blood cell that circulates around your body and is an important part of your immune system. T-cells scan for infection and abnormal cells throughout the body, including cancer and attack to kill these cells. They also help in the process for our immune system to remember these cells for future protection.
Chimeric antigen receptor (CAR) T-cell therapy is an emerging type of treatment in which a patient’s T-cells (a type of immune system cell) are taken from a patient’s blood. These cells are then changed in the laboratory. A special receptor gene called a chimeric antigen receptor (CAR) that binds to a certain protein on a patient’s lymphoma cells is added. Large numbers of CAR T-cells are grown in the laboratory and given to the patient as a one-time infusion. The CAR T-cells then find and attack the cancer cells.
KYMRIAH and YESCARTA CAR T-cell therapy products are approved and will be publicly funded in Australia. The patients who will benefit from this therapy are those who have relapsed (comes back) or refractory (does not respond to treatment) after at least 2 types of prior therapy. The lymphoma types that are currently funded include:
- Diffuse large B-cell lymphoma
- Transformed lymphoma and
- Primary mediastinal B-cell lymphoma
There are also clinical trials currently recruiting in Australia for other indications and subtypes.
Cell signal blockers
Cells receive signals that keep them alive and make them divide. These signals are sent along different signalling pathways inside the body. Blocking either the signal or a key part of the pathway can make cells die or stop the lymphoma from growing. Certain signalling pathways are more important in some types of lymphoma than in others. Scientists do not yet fully understand how all the various pathways are linked. Some examples of lymphoma treatments available currently include:
Bruton’s tyrosine kinase (BTK) inhibitors
Bruton’s tyrosine kinase (BTK) inhibitors work by blocking activity of a specific protein called Bruton’s tyrosine kinase (BTK). By blocking these protein BTK inhibitors may help move abnormal cells out of their nourishing environments in the lymph nodes, bone marrow and other organs where it gets excreted. BTK is also found in normal healthy B cells so this action of blocking may cause side effects. BKI inhibitors include:
PI3 kinase inhibitors
P13 kinase inhibitors work by inhibiting PI3K (phosphatidylinositol 3-kinase) which is an enzyme that is overactive in B-cell cancers. By blocking the effects of this enzyme, it affects the growth of malignant lymphocyte cells and causing cell death.
Programmed cell death inducers
Venetoclax is a targeted therapy that can make lymphoma cells undergo apoptosis. Apoptosis is the name given for programmed cell death. All normal cells undergo this process as part of the natural cell cycle process. This is where cells grow and die in an orderly way. In some cancers, it has been found that they are able to ‘turn off’ this process and cells grow uncontrollably.
Venetoclax switches off the survival signals that keep these cancerous cells alive when they should have died. This makes these cells now die.
Immune system modulators are therapies which enhance the body’s immune response against cancer. Some of these agents affect specific parts of the immune system, whereas others affect the immune system in a more general way.
Immunomodulators are believed to work by changing how the immune system works. They can do this in different ways, for example, by:
- Restoring some of the signals between immune system cells and lymphoma cells
- Blocking some of the signals within lymphoma cells.
An example is lenalidomide.
Lenalidomide works by activating the body’s immune system to target and kill the lymphoma cells. The medicine helps prevent the lymphoma cells from growing by cutting off their blood supply that they require to exist.
Histone deacetylase (HDAC) are proteins that help cells to grow and divide. Some cancers can alter the body’s immune system so that they are able to continue to grow in an uncontrolled way and do not die as they should. They in turn allow cancer cells to grow.
HDAC inhibitors block this activity by altering the genes to make cancer cells die. They also modify the body’s immune response to cancer cells and kill them.
Some examples of HDAC inhibitors include:
- Romidepsin (depsipeptide)
Romidepsin is isolated from a bacterium called Chromobacterium violaceum and is thought to reduce the growth and division of lymphoma cells by inhibiting the process involved in the regulation in these lymphomas.
Vorinostat is thought to work by reducing the growth and division of lymphoma cells, a process in the DNA which is involved in the gene regulation in these lymphomas.
Cytokine therapies are proteins or chemicals in our body that control the activity and growth of immune system cells. The two main cytokines in the body are interleukin and interferon:
- Interleukin works by stimulating anti-cancer T cells.
- Interferon works by helping the immune system slow the growth of cancer.
Interferon alfa-2b (Intron A®): a cytokine that targets the IFNAR1/2 pathway; approved for subsets of patients with follicular lymphoma