#6 Immune Checkpoint Inhibitors

Overview

The immune system’s collection of organs, special cells, and molecules is on constant alert to protect us from dangerous infection and disease and keep us healthy. It responds to antigens, or foreign bodies, in a highly coordinated process that employs several types of cells to circulate around the body, scanning for cellular abnormalities and infections.
 
Cancer, which kills approximately eight million people annually, is difficult to treat, let alone cure. Instead of treating cancer by just targeting the tumor for elimination, researchers have spent years exploring ways to harness the immune system and prompt it to do its job more effectively so as to recognize, fight, destroy, and remember cancer cells in the same way that it does with infectious agents.
 
More than a century ago, doctors suspected that the immune system had an effect on certain cancers but research in this area soon fell out of favor as surgery, radiotherapy, and chemotherapy became the backbone of oncology.
 
Recently, however, interest in using the body’s immune system in the war on cancer has been heightened by the remarkable results achieved by a class of drugs called immune checkpoint inhibitors. These intravenous immunomodulators effectively block the action of proteins that act as brakes, or checkpoints, on cells, which allow cancer cells to hide from the immune system and survive. Once freed by the special checkpoint inhibitors, however, this permits certain white cells of the immune system, the killer T cells, most notably, to carry out their lethal attacks on marauding cancer cells.
 
In one recent study of patients with advanced skin cancer, one third experienced 80 percent tumor shrinkage when given the combination of checkpoint inhibitors that block both the inhibitory action of CTLA-4 and PD-1 protein receptors on the surface of T cells. The T cells were rapidly mobilized by the drugs to hunt down and destroy tumors in patients with advanced melanoma, allowing them to live longer than ever before. This response was significantly different from that seen when either checkpoint inhibitor was used by itself.
 
This new immunotherapy drug class is stirring excitement not only because of significant long-term cancer remissions—cures, in some cases—but because of the novel way the drugs work by removing an immune system brake that cancer cells have cleverly exploited. It’s this unique approach of boosting the body’s own defenses that is producing stunning results, especially when checkpoint inhibitors are combined with standard anticancer therapies.
 
Researchers are now combining checkpoint inhibitors with either chemotherapy or radiation in treating lung cancer, gastric cancer, pancreatic cancer, kidney, and breast cancer. By directly killing cancer cells with radiation or chemotherapy, it’s hypothesized that the addition of immunotherapy will help create special T cells that will remain and will be able to recognize and kill any returning cancer cells long after the initial treatment has stopped.
 
Immunotherapy does not currently offer a cancer cure, but the novel checkpoint inhibitors have allowed doctors to make significantly more progress against advanced cancer than they had been able to achieve in decades.
 
With two drugs already approved for metastatic melanoma by the Food and Drug Administration (FDA), one of them two months earlier than expected, there is now increasing evidence that checkpoint inhibitors can work on a growing number of types of malignancies, including lung, kidney, bladder, ovarian, and head and neck cancers. Three pharmaceutical companies are expecting approval of their drugs by the FDA next year, while several others have clinical trials already in advanced testing stages.

 

Where Are They Now

Three immune checkpoint inhibitors have been approved for use in patients with melanoma with sales of over $1.5 billion in 2014. These immune checkpoint inhibitors have also been approved for use as an immunotherapy in lung cancer. There are over 80 companies researching 148 immune checkpoint inhibitors associated with various cancers, with 10 in the last phase of clinical trials. The checkpoint inhibitor cancer treatement industry is expected to achieve revenues of $16.55 billion by 2020.  A study started in 2012, however, revealed in 2016 that patients who take immune checkpoint inhibitors may be at higher risk of developing rheumatologic diseases, characterized by inflammation in the joints and soft tissue.

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