A common treatment used for lung cancer is immunotherapy. Immunotherapy drugs harness the body’s own immune system, allowing it to recognize and fight the cancer. Many immunotherapy approaches have proven to be effective against lung cancer. These can be applied as a second-line treatment — after another therapy, such as chemotherapy, has failed — or as a first-line, or initial, therapy. To date, most immunotherapy approaches have been tested in non-small cell lung cancer (NSCLC), with fewer therapies available for small cell lung cancer (SCLC).
The immune system and cancer
The body’s immune system includes a type of white blood cells (or lymphocytes) called T-cells. One role of T-cells is to identify, bind to and kill infected or abnormal cells such as cancer cells. However, in order to ensure that T-cells do not destroy healthy cells, immune system checkpoints are in place to stop them from indiscriminately targeting everything.
One of these checkpoint systems is the PD-1, or programmed cell death 1, pathway. Healthy cells produce a ligand — a small molecule that can bind to other proteins called receptors usually found on the surface of other cells — called programmed cell death ligand 1, or PD-L1. T-cells have a receptor (PD-1) that interacts with PD-L1, sending a message to block the killing of that cell.
Many lung cancer tumor cells hijack these inbuilt pathways to hide from the T-cells and escape being destroyed by the immune system, by producing PD-L1.
Targeted immunotherapy drugs
Currently, three approved immunotherapy drugs target the PD-1 pathway: Opdivo (nivolumab), Keytruda (pembrolizumab) and Tecentriq (atezolizumab). These drugs are antibodies, or proteins designed to identify and block a specific target. Keytruda and Opdivo both work by inhibiting the PD-1 receptor on the surface of T-cells. This prevents the cancer cells from evading the T-cells. Tecentriq is an antibody that identifies and blocks the PD-L1 ligand, which removes protection from the cancer cells and allows them to be targeted by T-cells.
These therapies help the immune system fight cancer. However, they are not specific to tumor cells. These treatments can remove the immune system checkpoint not only for the cancer cells but for healthy cells as well. As a result, T-cells may attack normal cells, causing potentially severe side effects.
Other therapies that target the PD-1 pathway are now in clinical trials to test their efficacy in lung cancer patients, for example, Imfinzi (durvalumab) and Bavencio (avelumab).
Ongoing clinical trials are also testing the effect of Yervoy (ipilimumab) in lung cancer patients, a drug previously approved to treat melanoma. This drug targets a different immune system checkpoint called the CTLA-4 pathway.
Other immunotherapy options
The targeted immune checkpoint inhibitors are the most common immunotherapy approaches in fighting lung cancer. However, other options exist. One example is cancer vaccines, which work by giving the immune system a boost to aid it in fighting off cancer. These are only available in clinical trials; examples include TG4010 (NCT02823990) and CimaVax (NCT02955290).
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