Hailed as one of the most exciting and unique cancer treatments of today, here’s everything you need to know about immuno-oncology.
The definition of immunotherapy is the use of the body’s natural defences (immune system) to fight disease. But, what is immuno-oncology? It's a type of immunotherapy that is specifically targeted to fight cancer. How does immuno-oncology work? This is the interesting bit! Immuno-oncology works by stimulating our immune system to fight back, when it wouldn’t usually be able to.
Normally, our immune system is able to destroy cancer cells in our body, however sometimes cancer cells can adapt and mutate, effectively hiding from our immune system. This is when tumours can develop and become a threat to our health. Immuno-oncology involves mobilising lymphocytes to recognise and eliminate cancer cells using the body’s immune system.
In theory, this is already much better for patients than the current treatments for cancer, which are principally surgery, chemotherapy and radiation. These treatments likely cause as much harm to patients as they do good, either leaving deadly cancer cells untreated, or killing off too many healthy cells in the body. Immuno-oncology allows cancer cells to be targeted, leaving the rest of the body unharmed. It also has far fewer limitations, being applicable to tumours at all stages of the disease with much higher efficiency and durability (meaning fewer recurrences!). Since the first immuno-oncology treatment was approved in 2010, it has proven effective in treating melanoma and lymphoma, as well as lung, kidney and bladder cancer.
So, what’s the latest on the immuno-oncology scene? What sort of treatments are currently available and what might be coming in the future?
Immune Cell Therapy (CAR-T)
Chimeric antigen receptor T-cell therapy (CAR-T), also known as an adoptive cell transfer (ACT), is a genetically-modified immuno-oncology treatment. In late 2017, the FDA advisory committee approved Novartis’ CTL019 unanimously, with one panel member Dr. Tim Cripe stating that the novel therapy is “the most exciting thing I’ve seen in my lifetime.” Novartis’ therapy is targeted at children with acute lymphoblastic leukaemia, a type of blood cancer.
CAR-T works by removing the patient’s cells, re-engineering them in the lab to produce CARs (chimeric antigen receptors) on the surface, and infusing them back into the patient via the bloodstream to attack the cancerous cells. They then remain in the body for a period of time to ward off recurrent cancer, resulting in long-term remission.
Monoclonal antibodies (mABs) and checkpoint inhibitors
The FDA has approved several monoclonal antibodies (mABs) treatments in recent years, namely trastuzumab (Herceptin) and alemtuzumab (Campath). This type of immuno-oncology therapy works by engineering antibodies, a type of protein, to target tumour-associated antigens, which will trigger an immune response to destroy cancer cells.
The brilliance of the immune system is that it can tell the difference between normal cells and harmful, foreign ones. It uses checkpoints to do so, that either turn up or turn down a signal. With cancer, tumours interfere with these signals to hide from immune responses.
The checkpoint protein PD-1 binds to another protein PD-L1 to stop T-cells from attacking other cells in the body. The trouble is, many cancers have an abundance of PD-L1 proteins which allows them to evade the immune system. Monoclonal antibodies can block this binding, boosting the immune response to kill off cancer cells. Examples of mABs that target PD-1 include nivolumab (Opdivo) which has been successful against cancers such as lung, kidney, bladder, head and neck, and pembrolizumab (Keytruda) which has been approved to fight melanoma and lung cancer.
The main issue with mABs is that they can cause quite serious side effects, especially when combined with chemotherapy drugs, so researchers are continuously working to reduce the risk associated with mABs. One of the notable risks is the immune response that comes with treatment, which is much like the fever people have when the body is fighting off bacteria or a virus, but worse. With immuno-oncology therapy, the immune response created can spark dangerously high fevers and produce more inflammation proteins within the body.
The science around cytokines is quite complex. In simple terms, cytokines are proteins that have a lot of control over the balance of the body’s immune response to an antigen. If there is an imbalance or their production is altered, this can lead to cancerous cell growth.
The Janus Kinase (JAK) family of proteins are a crucial part of this, leading researchers to develop a JAK inhibitor to stop these proteins from being excessively activated (which can cause tumours). JAK inhibitors have proved useful in treating cancers like renal cell carcinoma and melanoma, as well as autoimmune diseases such as rheumatoid arthritis, psoriasis and alopecia.
Cancer vaccines do not work in the same way as regular vaccines; their goal is not to prevent an infectious disease. Instead, they stimulate an immune response within the body to attack existing cancer cells. There are many types of cancer vaccine, with some containing tumour antigens, cancer cell DNA or immune cell activators.
Once injected into the patient’s bloodstream, cancer vaccines will activate the patient’s immune response to be able to fight the cancer. Like CAR-T, it is hoped that cancer vaccines may work for a while after being administered (thanks to the immune system’s great memory!), reducing the risk of recurrences.
Upcoming immuno-oncology therapies:
Kite Pharma, which has recently been acquired by pharma giant Gilead, is in the running with its own CAR-T therapy (KTE-C19) for aggressive B-cell non-Hodgkin lymphoma in adults, which is waiting on FDA approval. Kite Pharma is one of Novartis’ closest competitors. If approved and then successful with patients, this could completely change the way cancer is treated in the future.
Biotech Bluebird is teaming up with Celgene to develop a CAR-T therapy to fight multiple myeloma, but this is currently in early stages. The company as a whole, however, has a number of active and pre-clinical research programmes in the pipeline that focus on different cancers.
US-based biotech Juno Therapeutics is another company to watch, with a variety of immuno-oncology therapies in development. Their pipeline features therapies that target ovarian, B-cell non-hodgkin lymphoma and non-small cell lung cancer, among others.
We can also expect some breakthrough immuno-oncology therapies from some of the top 10 pharmaceutical and biotechnology companies in the world. Novartis, Celgene, AbbVie and Amgen all feature some exciting therapies in their oncology pipeline. See here a full list of upcoming immuno-oncology therapies and their stages of development.
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