CAR T Cell therapy is pioneering the future of anticancer treatment for Lymphomas, Myelomas and Leukemias.

What is Immunotherapy? New Golden Era of Anticancer Treatment

by Mackenzie Gignac

Immunotherapy has revolutionised the way haematological cancers are treated. Immunotherapy works by using the patient’s own immune system to fight against cancer cells. St. Vincent’s Hospital Clinical and Laboratory Haematologist Dr. Matthew Ku says that within our blood there are a variety of cells that help defend us against infections and cancers, such as T Cells and Natural Killer (NK) Cells. These cells act as “policemen” to detect and eliminate cancer cells before they can take hold in our body.

In cases where cancer occurs, the cancer is able to hide from these “policemen” T and NK Cells, or resist their attack. Immunotherapy refers to a group of treatments that work by helping these policemen cells by making them stronger, helping them “see” the cancer better, or by genetically modifying them into an “super-policemen” army capable of destroying cancer even if the cancer tries to resist and fight back.

Dr. Ku says that the idea of immunotherapy is to work towards making the immune system stronger while weakening the tumour cells. Furthermore, ‘immunotherapy is not just about immune and tumour cells; it’s about the tumour microenvironment as well.’

Dr. Ku says that immunotherapy treatments are not limited to just blood cancers. ‘Within Australia, immunotherapy is used prominently in treating other cancers such as melanomas.’

What types of immunotherapy treatments are available?

There are four main immunotherapy strategies currently available according to Dr. Ku.

1. Drugs that generally strengthen the immune system

Immunomodulatory drugs and CelMODS are examples of drugs that generally strengthen the immune system. These drugs stimulate a group of immune cells in the body called T cells and Natural killer cells, independent of their other activities against cancers. The generalised increase in immune functions means that there is better immune surveillance against cancers, and that there is a less likely chance that cancers can escape detection and destruction by the immune system. Dr Ku says that lenalidomide and pomalidomide are immunomodulatory drugs that are commonly used for multiple myeloma, a blood cancer that has seen many fantastic new therapies coming through.

Another class of drugs is called monoclonal antibodies, and they act by targeting the cancer cell surface structure. An example of this would be rituximab, which attacks the CD20 molecule on B cell lymphoma, and destroys the lymphoma cells via different immune mediated pathways.

2. Checkpoint Inhibition

Another immunotherapy strategy Dr. Ku mentioned is checkpoint inhibition. Immune checkpoints are a healthy part of the immune system. They work to regulate the body’s immune response so that it is not overactive unnecessarily, thus damaging healthy cells in the body.

Many cancers hijack this normal immune signal to hide themselves from the immune system. When checkpoint and partner protein on the cancer cell come together, they send an ‘off’ signal to T (policemen) Cells which can prevent one’s immune system from destroying the cancer cell. Checkpoint inhibitors work by stopping the checkpoint partner proteins on cancer cells from bonding with the checkpoint proteins on T Cells. These drugs prevent the ‘off’ signal from being sent which allows T Cells to kill off the cancer cells that appear in one’s immune system.

Dr. Ku says that checkpoint inhibitor immunotherapy is used to treat lymphomas, melanomas and lung cancers. Checkpoint inhibitors have shown to be effective against classical Hodgkin lymphomas. In effect, they yank away the “cloak of invisibility” that the cancer uses to hide itself, and allows the healthy immune cells to see and destroy the cancer.

3. T Cell Engagers

The third strategy Dr. Ku mentions isT Cell Engagers. These drugs are like guided missiles that directly bring the host’s immune cells next to the cancer cells. Dr. Ku describes the process, ‘T Cell Engagers are modules that hold onto T Cells with one arm and onto cancer cells with the other arm. This brings them together, creating T Cell immunity against the cancer cells.’

Dr. Ku has directly seen the positive results that have come from T Cell Engager immunotherapy clinical studies. ‘We at St. Vincent’s have a couple of studies using the T Cell engagers which have shown to be very effective. The results were even presented at one of the international lymphoma conferences last year,’ says Dr. Ku.

4. CAR T Cell Therapy

The fourth strategy that is at the forefront of immunotherapy is CAR T Cell therapy. Dr. Ku explains that CAR T Cell therapy works by collecting the patient’s own T Cells through an apheresis machine. Then the T Cells are genetically engineered to be super-strong, single-minded “super-policemen” that target cancer cells. An army of these cells are formed by growing them in the laboratory, and they are then reinfused back into the patient. However, ‘CAR T Cells are not widely available at the moment,’ urges Dr. Ku.

Amongst all these therapeutic options the CAR T and T Cell Engagers are some of the most effective treatment options available now, especially for diffuse large B cell lymphoma and follicular lymphoma. ‘T Cell Engagers and CAR T are cutting edge therapies for lymphomas and myeloma at the moment,’ says Dr. Ku. The number of clinical trials that focus on these two groups of agents will continue to grow exponentially. ‘We are at the start of the golden era in immunotherapies,’ says Dr Ku. ‘T Cell Engagers and CAR T are the new kids on the block, but they are also the ones that are attracting the most amount of interest because they appear to be the most effective.’

Dr. Ku says both CAR T and T Cell Engagers have their pros and cons. ‘CAR T works well, but has a higher risk of toxicity and side effects,’ says Dr. Ku. Harvesting the T Cells also requires more effort and can be more expensive. In comparison, T Cell Engagers might not be proven to be as effective yet, but they appear to be better tolerated, easier to administer and require less waiting time says Dr. Ku.

Are there any side effects?

Dr. Ku warns that there are unique side effects that might potentially come with CAR T and T Cell Engagers. Dr. Ku says that in his opinion, ‘standard chemotherapy treatments have more side effects’ than immunotherapy options. Dr. Ku says that patients may need to stay in the hospital for longer than chemotherapy because of the potential side effects.

1. Cytokine Release Syndrome - CRS

CRS is when the patient’s immune system is kicked into overdrive and starts to affect the other parts of the body, aside from the targeted lymphoma and leukemia cells. Dr. Ku says common CRS features include fevers, low blood pressure and low oxygen levels in the blood. As result, some patients might require intensive care support to manage a potential CRS symptom episode. However, Dr. Ku encourages that, ‘there are effective medications we can give to patients to control CRS.’

2. Neurotoxicity

Another main side effect that a patient might have to endure is neurotoxicity, which could affect higher centres within the brain thus hindering a patient’s speech or ability to write. ‘Some people will need neurological support or management from the neurologist because of neurotoxicity.’ Again, Dr. Ku advises that doctors do have the resources to help manage this side effect. Additionally, in terms of brain function CAR T and T Cell Engagers are not known to have any long-term, permanent adverse effects.

Which Immunotherapy treatments have been approved on the Pharmaceutical Benefit Scheme (PBS) in Australia?

In Australia, PeterMac is the only hospital that is conducting publicly funded CAR T therapies. Otherwise, all other CAR T therapies are being done as clinical trials at select institutions.

Dr. Ku advises that there are no publicly funded T Cell Engager treatments.

‘Lenalidomide and Pomalidomideare funded by PBS for myeloma,’ says Dr. Ku.

In regards to checkpoint inhibitors they are currently funded for Hodgkin lymphoma says Dr. Ku.

Where can I go if I have lymphoma and I am interested in considering new immunotherapies?

Dr. Ku says there is good news for cancer patients here in Australia. ‘This is the new era of cancer therapy. In Victoria in particular there are many big centres conducting immunotherapy trials,’ encourages Dr. Ku.

If you are a patient who is looking for novel treatment options, Dr. Ku advises you to contact your specialist about the trial options available. At Melbourne Blood Specialists our doctors can link you up to the appropriate health centre for blood cancer treatment. If you are interested in exploring the option of immunotherapy please contact us at Melbourne Blood Specialists today.