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| James Allison and Tasuku Honjo |
American James Allison and Japan's Tasuku Honjo have won the 2018 Nobel Prize in Medicine for a pioneering approach to cancer treatment. The pair received the prize for their work in harnessing the body’s immune response to attack cancer cells.
Dr. James Allison studied a protein that acts as a brake on the immune system to mount a response against the cancer cells. He developed a way to “release the brake” so as the immune system could attack cancer cells.
Dr. Tasuku Honjo also discovered a similar protein that prevents the cells to attack cancer cells, but the mechanism is different. Therapies based on this joint discovery led to the development of an entirely new class of drugs called ‘checkpoint inhibitors’ have revolutionized the cancer immunotherapy.
Several scientists have observed that T-cell protein CTLA-4 blocks the T-cell from attacking the cancer cells. Working at his laboratory in University of California, Berkeley, James P. Allison developed an antibody that could bind to CTLA-4 and block its function. After performing animal studies, in 2010, a human study showed promising results in patients with advanced melanoma.
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Figure: Upper left: Activation of T cells requires that the T-cell receptor binds to structures on other immune cells recognized as ”non-self”. A protein functioning as a T-cell accelerator is also required for T cell activation. CTLA- 4 functions as a brake on T cells that inhibits the function of the accelerator. Lower left: Antibodies (green) against CTLA-4 block the function of the brake leading to activation of T cells and attack on cancer cells.Upper right: PD-1 is another T-cell brake that inhibits T-cell activation. Lower right: Antibodies against PD-1 inhibit the function of the brake leading to activation of T cells and highly efficient attack on cancer cells.
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In 1992, few
years before Allison discovered T-cell protein CTLA-4, Tasuku Honjo discovered
PD-1, another protein expressed on the surface of T-cells. Further research
showed that PD-1 also functions as a T-cell brake like CTLA-4 but via a
different pathway. After animal studies were successful, clinical study in
humans showed promising results leading to long-term remission and a possible
cure in several patients with metastatic cancer, a condition that had
previously been considered virtually untreatable.
We now know
that the drugs called “immune checkpoint therapy” have fundamentally changed
the way certain cancers are treated.
Example of
CTLA-4 inhibitor includes Ipilimumab (Yervoy), used to treat melanoma of the
skin and some other cancers. PD-1 Inhibitors include Pembrolizumab (Keytruda),
Nivolumab (Opdivo), and Cemiplimab (Libtayo).
These drugs
have been shown to be helpful in treating several types of cancer, including
melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder
cancer, head and neck cancers, and Hodgkin lymphoma. They are also being
studied for use against many other types of cancer.
New clinical
studies indicate that combination therapy, targeting both CTLA-4 and PD-1, can
be even more effective, as demonstrated in patients with melanoma.
Checkpoint
therapy has now revolutionized the way we view how cancer can be managed. It
has already prolonged life of millions of people with cancer worldwide.
Here is a
short video about Dr. Jim Allison of MD Anderson Cancer Center:
Also, here
is an earlier video of Dr. Tasuku Honjo discussing some of his work
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