Only a few years after James P. Allison’s breakthrough immunotherapy treatment, now known as ipilimumab, Professor Tasuku Honjo was in Kyoto, Japan discovering an equally important protein on immune cells. His discovery proved to be strikingly effective in the fight against cancer.
Tasuku Honjo and his team identified PD-1 —another molecule that influences T cell activity.
Careful exploration of the protein’s function, eventually revealed that it also operates as a brake like Allison’s cytotoxic T lymphocyte antigen-4 (CTLA-4), but with a different mechanism of action.
PD-1 sticks to a molecule on cancer cells called PD-L1. This interaction causes the immune cells to ignore the tumour cell. And drugs stopping this molecular ‘handshake’ help reveal tumour cells to the immune system, allowing T cells to attack and kill the cancer cells.
Thanks to these two scientists, and the teams of researchers involved, many companies are now developing drugs that block CTLA-4, PD-1 and PD-L1. And the hunt for other similar molecules continues.
Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are the first therapies to come of Honjo’s discovery.
Keytruda is manufactured by Merck & Co to treat advanced melanoma; non-small cell lung cancer; head and neck squamous cell cancer. Global sales are reported to be $7.2 billion.
Opvido is Manufactured by Bristol-Myers Squibb and Ono Pharmaceutical to treat non-small cell lung cancer; metastatic melanoma; renal cell carcinoma; classical Hodgkin lymphoma. Global sales are reported to be: $1.8 billion
They both target the PD-1 molecules on the surface of T cells. In doing so, it releases the ‘brakes’ on the immune cells so they can find and kill cancer cells.
In many cases, these drugs are still being tested in clinical trial. But, for some advanced cancers, they have already saved lives.
Allison and Honjo were awarded the Nobel Prize for Physiology or Medicine 2018 “for their discovery of cancer therapy by inhibition of negative immune regulation.”
The duo’s discoveries have revolutionised our understanding of how the immune system sees cancer. Both Nobel Lauriants have shown how different strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer and the seminal discoveries by both constitute a landmark in our fight against cancer.
Tasuku Honjo was born in Kyoto, Japan and studied medicine at Kyoto University receiving his PhD there in 1975. During the 1970s he also worked in the United States at the Carnegie Institution of Washington in Washington, DC, and at the National Institutes of Health in Bethesda, Maryland, with which he also was later associated as a visiting research fellow.
In Japan he has worked at Tokyo University, Osaka University and Kyoto University, where he has been a professor since 1984.Tags: cancer, cancer research, cancer treatment, CAR-T, cell therapy, immunotherapy, japan
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