Immune Check-point Inhibitors (ICI): a non T specific immunotherapy

The research in immunotherapy focused on receptors (called CTLA4, PD1, PD-L1) able to remove the brakes blocking T cytotoxic lymphocytes and preventing them from attacking the tumors. This non-specific approach led, in 2011, to bring to market an anti-CTL-A4 against metastatic melanomas. It proved to be efficient for 10 to 15% of the patients on the long term. Two anti-PD-1 have been developed and registered in 2014. They bring up to 30% of partial or complete response on several types of tumors. An anti-PD-1 has also been registered in the USA and in Europe for a certain category of lung cancer.

Since 2015, three ICI treatments inducing a non specific activation of T-lymphocytes by removing the breaks have been registered in 2nd line of NSCLC: nivolumab (Opdivo®, Merck), pembrolizumab (Keytruda®, Merck) and atezolizumab (Tecentriq®, Roche) in patients expressing PD-L1 (PD-L1 is expressed in about 20% of patients).

In 2016, a first treatment was registered in 1st line treatment: pembrolizumab (Keytruda®, Merck) in patients expressing PD-L1.