Over the past 10 years there have been major advances in immunotherapy. Although still in the early stages of development, it is quickly becoming one of the most significant forms of therapy to treat cancer. Given the huge potential of immunotherapy, Big Pharma and biotech are heavily invested in R&D, tracing the next breakthrough.
Major strides have been made within the area of immunotherapy since 2010, when promising results showed remarkable effects in patients with advanced melanoma skin cancer. In fact, several patients even showed signs that their cancer had disappeared.
As of 2010, immunotherapy was approved to treat patients with widespread melanoma. Later research showed that the antibody has a much broader effect for patients with many different forms of cancer. According to Inge Marie Svane, professor and head of the Centre of Cancer Immunotherapy at Herlev Hospital: “Immunotherapy is fast becoming one of the biggest forms of cancer treatment. Obviously surgery, chemotherapy, and radiation remain the major treatments in hospitals, but immunotherapy is developing incredibly fast. Right now, immunotherapy is used as a treatment for around 15 different forms of cancer.”
I don’t think all forms of cancer can be treated with immunotherapy, but we will see a rather high number of cancer forms being treated with immunotherapy in the future
Inge Marie Svane
Prior to these advances, an efficient treatment for advanced melanoma had been lacking as this form of cancer is not particularly responsive to chemotherapy. Moreover, the immune systems of patients with melanoma are less compromised. A leading hypothesis was that there may be an interaction between melanoma cancer cells and the immune system that could be taken advantage of. Enthusiastically, Svane shares: ”It turned out to be true and melanoma is the type of cancer where we see the most effect.”
2018 Nobel Prize
In 2018, the Nobel Prize in Physiology and Medicine was jointly awarded to James P. Allison (from the United States) and Tasuku Honjo (from Japan) for their discovery of an effective cancer treatment that inhibits negative immune regulation. Through their research, the Nobel laureates established an entirely new form of cancer treatment by stimulating the inherent ability of the immune system to attack tumor cells.
“The breakthrough came after a change of strategy. Previously, researchers had tried to accelerate reactions of the immune system with some effect in patients with melanoma and kidney cancer,” explains Svane.
Instead of accelerating reactions in the immune system, Allison and Honjo began to study proteins that function as a brake. Whereas Allison studied the T-cell protein CTLA-4, Honjo studied the PD-1 protein expressed on the surface of T-cells. Although CTLA-4 and PD-1 operate through different mechanisms, they both function as a kind of brake in the immune system.
Elaborating on this process, Svane explains: “Cells in the immune system, primarily T-cells, attack and eliminate the cancer, but can be blocked by immune checkpoints. The antibodies that were developed allow immune cells to stay activated and respond more effectively to the cancer cells.”
Now, less than 10 years after Allison and Honjo’s breakthrough, most major pharmaceutical companies have an immunotherapy pipeline and are heavily involved in the research and development of new compounds. For her part, Svane has initiated more than 15 phase I, II, and III immunotherapeutic trials as a principal investigator since 2001, and points to the growth of the field: “More than 3,000 different compounds are under development, covering more than 60 different mechanisms.”
Clinical trials that are currently in progress include established antibodies being tested on new patient groups, in combination with standard treatments (such as chemotherapy, CTLA-4, and PD1) as well as a whole wave of new immune-regulating proteins.
From Svane’s perspective: ”The pharmaceutical industry has realised that immunotherapy represents a huge market potential if they develop a really effective immunotherapy compound, just as it has major benefits for cancer patients.”
Compared to other therapies, immunotherapy can offer long-term survival among advanced-stage patients who show good treatment effects. According to Svane, these patients continue to benefit from immunotherapy for years without the relapse that is common with more traditional therapies like chemo.
It is important to emphasize that research and development in immunotherapy remains in its infancy and will continue to grow in the coming years. In Svane’s words: “Right now, roughly 15 forms of cancer can be treated with immunotherapy, including solid forms of cancer and different types of blood cancer. I don’t think all forms of cancer can be treated with immunotherapy, but we will see a rather high number of cancer forms being treated with immunotherapy in the future.”
Last year, the first approval was granted to use the PD-1 antibody as a preventive treatment against relapses for patients with melanoma.
Svane is careful to point out that this is for situations where patients do not have a widespread disease but may have had, say, a birthmark removed: ”Perhaps the cancer spread to local lymph nodes, which will then be removed and further treated with PD-1 to prevent a relapse. In those cases, we have seen that the risk of relapse was reduced by almost 50 per cent. This is quite remarkable.”
These results do not come without a cost, however. Just like chemotherapy and radiation, immunotherapy comes with its share of adverse side effects. According to Svane, ”Some side effects are rather serious, or even life-threatening, so it’s important for the patient to get the right care. Life-threatening side effects are very rare but may happen if the immune system becomes too active, too aggressive, and attacks the body’s different organ functions.”
To gain more insights, large clinical trials are being conducted to identify which patients stand to benefit the most from immunotherapy. They are also seeking to establish when immunotherapy is better – or worse – than other leading therapies, and the extent of side effects.
Giving Svane the last word: “Many factors, or patterns of factors, will determine whether immunotherapy is effective, but not all factors have been established. The number of mutations present in cancer cells may also play a role. The more mutations, or genetic faults, the greater the likelihood for an effective immunotherapy.”