Immuno-oncology

Immuno-oncology: The next generation of cancer treatment

More than 30 years ago, researchers discovered that the body's own immune system is capable of curing certain types of cancer itself under certain conditions. This potential is being exploited in a targeted manner in the context of new types of immune therapies. The strongest weapon in this regard is certain defense cells of the immune system, the so-called T-cells.

T-cells fight off intruders such as bacteria and viruses in the body. In this way, they help to prevent and cure diseases. In addition, under certain circumstances, T cells can recognize and destroy cancer cells that are produced naturally in the body.

Malignant cancer cells very often develop mechanisms by which they can suppress an immune response or remain undetected by the immune system.

Our immune system protects us not only from bacteria and viruses, but also from degenerated body cells. Every day, our immune system removes these outliers to prevent the development of cancer. But cancer cells are adept and can learn to avoid elimination by the immune system. This is where immuno-oncology comes in: with the help of appropriate methods and active substances, our own defense cells can recognize and effectively destroy cancer cells again.

Cancer therapy is about to change

Surgery, radiation, chemotherapy – these methods are still the most commonly used procedures in the fight against cancer today. However, radiation and chemotherapy are associated with numerous side effects. After all, both are not only effective against malignant cancer cells, but also against the body's own healthy tissue. Toxic and radioactive substances for example destroy cancer cells in a more targeted manner if they are conjugated to antibodies that bind to a specific structure on the surface of tumor cells.^1,2

In targeted therapies, researchers identify structures, which occur primarily on cancer cells. These are created by mutations in the genome of a developing cancer cell. On one hand, this allows the tumor to be destroyed in a targeted manner, while on the other hand it is increasing the pressure on cancer cells to adapt further in order to avoid elimination. This can lead to cancer cells remaining undetected. This is not the case with the methods of immuno-oncology.³

Importance and discovery of immuno-oncology

While targeted cancer therapies affect the tumor cell directly, immuno-oncology activates the patient's immune system to fight cancer.⁴ The idea of immuno-oncology was born by coincidence. Back in 1867 in Bonn (Germany), after the tumor of a female patient shrank after she had been transferred to the bed of a gangrene* patient, it was already suspected that the body's own defense system could attack and eliminate cancer.⁵ The contact with bacteria of the skin infection apparently led to the activation of the patient's immune system. More than 140 years later, research in the field had progressed so far that immuno-oncology was named the scientific breakthrough of the year 2013 by the scientific magazine "Science".⁶

*Gangrene refers to the death of body tissue due to either a lack of blood flow or a serious bacterial infection.

Mobilizing the body's own immune system

Therapeutic approaches of immuno-oncology can be specifically directed against the tumor or have an undirected effect. In non-specific immunotherapy, the immune system is generally activated in order to act more effectively against foreign bodies, pathogens and degenerated cells.⁷.

The method of checkpoint inhibition also belongs to non-specific immuno-oncology. It prevents cancer cells from disguising themselves as healthy tissue and thereby escape their elimination. For this purpose, specific proteins on the surface of T cells (checkpoints) are blocked. Otherwise these proteins would bind to tumor cells and classify them as harmless. However, immune checkpoints are also used to recognize the body's own structures. When checkpoints are blocked, the immune system may no longer tolerate healthy cells but also eliminate them, which may lead to autoimmune side effects.⁸

T cells: an effective weapon against cancer

In contrast to non-specific immunotherapy, the increased immune response of targeted immunotherapy is specifically directed against cancer cells. Thereby, the focus is on one group of defense cells: T cells.⁷

T cells have a strong cytotoxic effect and can eliminate cancer cells naturally. However, tumor cells can escape recognition by T cells through adaption. Therapeutic approaches in immuno-oncology therefore aim to enable T cells to identify cancer cells and classify them as a danger to the organism.

One method is the Chimeric Antigen Receptor therapy (CAR-T cell therapy), in which some of the patient's own T cells are extracted. Outside of the body, they are genetically modified in order to recognize and destroy cancer cells more efficiently. They are then returned to the patient, called adaptive T cell transfer.⁹ CAR-T cells remain active in the body for a long time and therefore must act selectively against degenerated cells without destroying healthy tissue. The therapy is part of personalized medicine and must be adapted to each patient individually.¹⁰

Another innovative approach is the BiTE® technology. In this therapy the biotechnologically produced bispecific molecules bind simultaneously to a cancer cell and to a T cell. They serve as a bridge between the cells and enable the T cell to attack the tumor cell directly.^{10, 11}

Viruses can destroy tumor cells

Today, researchers are not only taking advantage of the characteristics of the immune system, but also of those of viruses in the fight against cancer. This is possible because it is in the nature of viruses to attack cells and multiply inside them. In laboratory, viruses can be genetically modified, so they only infect cancer cells and not healthy cells. These oncolytic viruses can also manipulate the biological processes of cancer cells and stimulate the production of certain signal molecules and tumor-specific structures of antigens.^12,13

After being infected, the oncolytic viruses multiply inside the tumor cells until they finally burst. The viruses are released and able to infect new cancer cells. In addition, immune cells are attracted by signal molecules. They are supposed to recognize the tumor-specific antigens and attack cancer cells elsewhere in the body carrying the same antigen.¹³

Combination of different therapy options

The methods of immuno-oncology are gaining in importance. With growing diversity, the possibilities to combine different approaches in immuno-oncology are also increasing. This is constantly being researched as our own body’s defense mechanism, our own weapons to beat cancer, offer new therapies for cancer patients.

References

1. Akbari, Bahman, et al. "Immunotoxins in cancer therapy: Review and update." International reviews of immunology 36.4 (2017): 207-219.
2. Scott, Andrew M., Jedd D. Wolchok, and Lloyd J. Old. "Antibody therapy of cancer." Nature reviews cancer 12.4 (2012): 278-287.
3. Shekarian, Tala, et al. "Paradigm shift in oncology: targeting the immune system rather than cancer cells." Mutagenesis 30.2 (2015): 205-211.
4. Hughes, Paul E., Sean Caenepeel, and Lawren C. Wu. "Targeted therapy and checkpoint immunotherapy combinations for the treatment of cancer." Trends in immunology 37.7 (2016): 462-476.
5. Busch, W. "Aus der Sitzung der medicinischen Section vom 13 November 1867." Berl Klin Wochenschr 5 (1868): 137.
6. Couzin-Frankel, J. “Cancer Immunotherapy” Science (2013)
7. Monjazeb, Arta M., et al. "The role of antigen-specific and non-specific immunotherapy in the treatment of cancer." Journal of immunotoxicology 9.3 (2012): 248-258.
8. Thallinger, Christiane, et al. "Review of cancer treatment with immune checkpoint inhibitors." Wiener Klinische Wochenschrift 130.3-4 (2018): 85-91.
9. Wang, Xiaoping, et al. "Humanized anti-EGFR antibody panitumumab inhibits tumor growth of inflammatory breast cancer by inducing antitumor immunity." (2019): 4492-4492.
10. Choi, Bryan D., et al. "Bispecific antibodies engage T cells for antitumor immunotherapy." Expert opinion on biological therapy 11.7 (2011): 843-853.
11. Gregory, Richard C., et al. "The anti-TGFβ neutralizing antibody, SAR439459, blocks the immunosuppressive effects of TGFβ and inhibits the growth of syngeneic tumors in combination with anti-PD1." (2018): 2790-2790.
12. Gujar, Shashi A., and Patrick WK Lee. "Oncolytic virus-mediated reversal of impaired tumor antigen presentation." Frontiers in oncology 4 (2014): 77.
13. Lawler, Sean E., et al. "Oncolytic viruses in cancer treatment: a review." JAMA oncology 3.6 (2017): 841-849.