Ayesha Javid discusses the impact of Dr. James P. Allison and Dr. Tasuku Honjo’s findings in cancer therapy and research.
The term cancer is the uncontrolled proliferation and migration of cells spreading to the distant organs. In the global perspective, cancer is a major medical challenge, killing millions of people each year. The Nobel Assembly at Karolinska Institute awarded the 2018 Nobel Prize in Physiology or Medicine, jointly, to James P. Allison and Tasuku Honjo for establishing an entirely new principle for cancer therapy. According to their research, our immune system can be recruited in a way to fight against the cancer cells, consequently revolutionizing the entire therapeutics of the cancer.
There are three pillars in the cancer treatment: surgical removal, radiotherapy and chemotherapy. During the last 50 years, treatment of cancer has improved considerably, yet, every year, millions of people die of cancer. Hence, more types of treatment are desperately needed. Much research has been devoted to finding more treatment options for cancer, and one area of interest is harnessing one’s immune system to attack cancer cells.
Our immune system is comprised of a great diversity of cells and molecules, which protects us from infections. The fundamental property of this system is its ability to discriminate between ‘self’ and ‘non self.’ In our immune system, T cells are the soldiers that fight against all sorts of foreign invasions, such as bacteria and viruses. Research has shown that there are molecules on the surface of the T cell, called ‘brakes’, which, when pressed, prevent the T cell from performing its function. This is the reason that our immune system does not recognize the cancer cell as a foreign invader. One of the brakes is CTLA-4, discovered by Dr. Allison and his team. Allison developed an antibody for CTLA-4, which blocks the brake. As a result, T cells are released from the brake, become more active, and consequently attack the cancer cells. These key experiments showed spectacular results. The mice who were given this CTLA-4 antibody were cured from their cancer. A biotechnology company produced the human antibody against CTLA-4. In 2011, after several successful human trials, treatment was approved for inoperable metastatic melanoma.
Meanwhile in Japan, several studies in this direction were already being performed. In 1992, Dr. Honjo discovered a new protein on the surface of a T cell, which he called PD-1. After several years of research, he concluded PD-1 also acted as a brake, similar to CTLA-4. He found out that PD-1 is also expressed on Antigen presenting cells and cancer cells. In order to scientifically prove that the blockade of this PD-1 brake by an anti- PD-1 antibody could also unleash the T-cell response against cancer, he performed various studies on malignant melanoma with liver metastasis in mice. The results showed that the mice had no metastasis after the antibody was introduced. Hence, he predicted that anti- PD-1 treatment might complement anti- CTLA-4 treatment. He also predicted that anti -PD-1 might give less side effects. Honjo then turned to pharmaceutical companies. An intensive program was started by other scientists mainly in the USA which gave similar and even more better results not only for melanoma patients but for other types of cancer as well. In 2014, Food and drug administration (FDA) approved the anti PDA-1 treatment for melanoma. In 2015, it was approved for lung and kidney cancer. Both of these studies gave birth to a new concept in immunotherapy called immune checkpoint inhibition.
These researches gave a completely new tool to add to the toolbox, thereby revitalizing the whole area of cancer treatment. All previous cancer treatment were directed against the tumor cells. This checkpoint inhibition therapy is unique as it is embarks that our inherent immune system can be used and directed against the cancer, hence providing treatment to a wide variety of tumors. The side effects of this therapy are manageable and reversible, giving a positive benefit risk balance.
Many different studies are working to find new checkpoints inhibitors. The future beholds a more individualized therapy of finding the right combination for the right cancer and for the right patients, thereby combining the conventional treatment options with this new therapy.