…antibodies are allowing the immune system to destroy cancer cells.
By Paul Conkling, MD
Virginia Oncology Associates
On March 6th, President Jimmy Carter stood before one of the Sunday school classes he teaches in Plains, Georgia, and shared a remarkable piece of information. He announced that he no longer needed treatment for cancer – less than seven months after revealing he had been diagnosed with melanoma that had metastasized to his brain.
For oncologists, the news was less of a surprise than a confirmation. The President had been treated for his aggressive cancer with a new drug, pembrolizimab (Keytruda), which was approved not long before his diagnosis.
Pembrolizimab is an example of a group of new therapies – checkpoint inhibitors, or antibodies that modulate the immune system, allowing the immune system to do a better job of finding and killing cancer cells.
We’ve known for at least 25 years that certain cells in the immune system (T cells) have the ability to infiltrate into tumors and kill cancer cells. These T cells develop receptors that are unique to the particular cancer cell; they attach to the cancer cell and literally punch a hole in the cell, killing it. However, while the process has worked well in the test tube, that success hasn’t translated to human beings in real time – until now.
In the last five or six years, because of improved molecular genetic techniques, we have a better understanding of why it hasn’t worked: it’s because of a set of proteins called PD-1 and PDL-1, which work together to protect or hide the tumor cell from the T cell, so the cancer cell has in effect masked itself from the normal immune system, preventing the T cells from entering and killing the tumor cell.
There are now a number of pharmaceutical companies that are producing a variety of anti-PD-1 and anti-PDL-1 antibodies. We’re using these therapies every day now, some as part of clinical trials, and some commercially. Two of these antibodies are currently approved by the FDA: pembrolizimab, which President Carter used, and nivolumab (Opdivo.) The FDA approval is for just three diseases: non-small cell lung cancer, metastatic melanoma and renal cell carcinoma.
It’s very likely, however, that these two drugs will soon be approved to treat cancer of the urinary bladder, squamous cell carcinoma of the larynx or tongue, stomach and esophageal cancers, triple negative breast cancer and ovarian cancer.
A word of caution: these therapies, while more effective than anything we’ve seen for the last few decades, don’t work for everyone. But when they do, they produce very dramatic responses – and from what we’ve observed, very durable, long-term responses.
We are at the dawn of a new age in oncology care, with so many new avenues of treatment being developed, giving us new ways to treat disease. It’s a very exciting time.
Paul Conkling, MD is a graduate of Dartmouth College and the Ohio State University College of Medicine. He is involved in Hematology/Oncology research and currently serves as the coordinator for the Clinical Oncology Research Program at Sentara Hospitals in Norfolk, Virginia. He is a consulting associate for the Department of Medicine at Duke University, as well as a Clinical Assistant Professor at Eastern Virginia Medical School.
