The 2018 Nobel Prize in Physiology or Medicine has been awarded to James Allisson and Tasuku Honjo for their research about immunotherapy to treat cancer. This therapeutic strategy is based on immune checkpoint targeting.
Immune checkpoints are regulators of the immune system. Cancerous cells can use them to protect themselves from attacks by the immune system. Consequently immune checkpoints are an interesting target for oncotherapy.
Allisson and Honjo worked independently on two immune checkpoints, CTLA-4 protein and PD-1 protein respectively. CTLA-4 protein prevents T-cell to attack cancerous cells. James Allison has studied this protein and has engineered an antibody (ipilimumab) that can bind CTLA-4 and restore T-cell efficacy. PD-1 is another checkpoint; this protein present on T-cell interacts with a tumor cells protein, PD-L1, which blocks programmed death of cancerous cells. Anti-PD-1 or anti-PD-L1 molecules prevent T-cell inactivity and are therefore drug candidates of choice.
These therapeutic strategies are innovative because they do not target directly cancer cells like previous strategies, but rather the brakes of the immune system. Clinical trials demonstrated an efficacy of ipilimumab in 11% of patients with melanoma, leading to their approval in 2011. It is the first immune checkpoint inhibitor approved by the US Food and Drug Administration. Concerning anti-PD-1 therapy, clinical trials demonstrated responses in several kinds of cancer, including lung cancer which is the most deadly. Indeed the therapy was effective in 18% of patients with lung cancer, 28% of patients with melanoma and 27% of patients with kidney cancer. A major advantage of this strategy is that it is not specific, therefore it can be used to treat different cancers. Moreover survival is longer with immunotherapy compared to other treatments. Recent clinical tests showed that combined therapies targeting both CTLA-4 and PD-1 might also be a promising strategy.
Congratulations to James Allisson and Tasuku Honjo !
Now the priority is to identify biomarkers to predict who will respond to the immunotherapy. Many works also focus on the research of new immune checkpoint inhibitors.
HCS Pharma is aware of the therapeutic potential of immunotherapy: we are developing 3D in vitro models with co-culture of cancerous and immune cells to study cells interactions and drug responses!