Using the body’s own defenses against cancerous tumors has been the virtual “Holy Grail” for oncology researchers. One of the primary challenges in this field of study lies in the fact that cancer cells are not foreign pathogens. Rather, they are native cells that have mutated in such a way that they no longer go through apoptosis or natural “cell death.” Therefore, antibodies do not normally recognize them as invaders. In recent years, however, researchers have been finding various ways to use the body’s own immune defenses against cancer. The most recent breakthrough in this area involves a class of drugs known as checkpoint inhibitors.
These “checkpoints” are proteins that identify a cell and whether its a normal part of the body’s system or a pathogen invading from outside. Killer T-cells – the front line of the immune system – literally “check” these identifiers in order to determine whether or not the cells in question represent a threat, such as an infection. However, cancer cells, behaving like virtual “identity thieves,” are able to appropriate these immune checkpoints and use them to hide from T-cells. Checkpoint inhibitors are able to rip away this protein “mask” and reveal a cancer cell’s true identity – clearing the way for an attack by the immune system.
There are a number of checkpoint inhibitors on the market today, some of which target the mechanism that T-cells (PD-1) use to determine whether a cell is benign or malignant. These include pembrolizumab (Keytruda) and nivolumab (Opdivo). Other drugs in this class include atezolizumab (Tecentriq), avelumab (Bavencio) and durvalumab (Imfinzi). These drugs act to inhibit the checkpoint proteins present on target cells (PD-L1).
Keytruda, a product of Merck Oncology, was approved by the FDA last year as a first-line treatment for adenocarcinoma, or non-small cell lung cancer – the most common form of the disease, accounting for approximately 75 percent of all cases. Until now, however, oncologists have been hesitant to use it because a limited study failed to show any benefits in extending survival rates. However, a recent study from the Perlmutter Cancer Center at New York University has demonstrated that Keytruda, administered in conjunction with standard chemotherapy treatments, can improve patient survival by as much as 100 percent.
The study involved 616 chemotherapy patients. Half of the group were given Keytruda. Those in the control group were allowed to take the drug if their cancer got worse. After twelve months, 69 percent of the Keytruda group were still alive as opposed to 49 percent of those who received chemotherapy alone. The study also found that adding Keytruda to the chemotherapy regimen delayed metastasis by an average of nine months.
There was a downside: 4 percent of the Keytruda group wound up developing lung inflammation, with three participants dying as a result. Nonetheless, the results are promising enough that many physicians believe the use of immunotherapy drugs will eventually become the new standard of treatment.