2018 Nobel Prize: Before the Prowess of James Allison Came an Inserm Discovery

Institute

The research receiving this year's Nobel Prize in Medicine is partially based on a discovery made in 1987 in the laboratory of Inserm Research Director Pierre Golstein. Indeed, it was his team at the Center of Immunology of Marseille-Luminy which was the first to identify protein CTLA-4 – a current target in some immunotherapy strategies in the treatment of cancer.

A new member of the immunoglobulin superfamily: CTLA-4. Published July 16, 1987 in the journal Nature, this research by Pierre Golstein and his team at the Center of Immunology of Marseille-Luminy* has been mentioned several hundred times in the scientific literature. This publication also underlies that of James Allison which has been awarded a Nobel Prize this year.

Golstein and his team were interested in the mechanisms of cell death induced by immune system cells known as the cytotoxic T-cells. They analyzed these "killer" white blood cells in depth in their search for "molecular weapons" enabling them to eliminate cells which are potentially harmful to the body (infected cells, cancer cells, etc.). While this research did lead them to identify the arsenal in question, it also led to the discovery of other compounds produced by the lymphocytes, in particular CTLA-4.

It was not until a few years later that other researchers set about the functional characterization of this protein produced by the lymphocytes, and even longer for James Allison to develop the therapeutic approach based on the inhibition of its activity.

CTLA-4 and immunotherapy in the treatment of cancer

While the T-cells are capable of attacking cells which are potentially harmful to the body, their activity is controlled by various "regulators", of which CTLA-4 is one. This protein slows the anti-tumor activity of these immune cells. The idea developed - with success - by James Allison consists of removing this effect by using specific antibodies to block the activity of CTLA-4.