Immunotherapy for cancer has finally come of age.
Over the past 50 years, physicians and scientists have learned that the body is always forming “malignant” cells, those cells that are inappropriately growing within an organ that has a defined and predictable cellular function and growth pattern. Take the melanocyte for example, those freckled areas on the skin that form melanin, the skin’s pigment. When these cells begin to reproduce inappropriately they become Malignant Melanoma. It is likely that many of the early melanoma cells either die spontaneously or the immune systemic eradicates them. Sometimes, however, they avoid the immune system, multiply and metastasize. Historically, we known that on occasion melanoma can go into spontaneous remission, and sometimes despite surgery, the same melanoma can recur 10, 20 and even 30 years later. Our current thinking is that the immune system keeps those melanoma cells in check, however, some time later in life, that “immunosurveillance” fails and the cancer recurs.
One of the exciting immunotherapies for metastatic melanoma has been the use of high dose interleukin 2 (IL-2) that can induce a remission in patients by stimulating the immune system. Although its success is usually less than 10%, the remission can be very dramatic; however the side effects can be life-threatening.
As the mechanisms for immune regulation have become understood, we recognize a system of so-called “check points” that help to turn on or damp down the immune system. These “check points” help to differentiate self from non-self. Unfortunately many cancer cells use these same check points to turn off the immune system. There are more than 50 such check points described but two important ones are PD-1 (programmed death -1) and CTLA-4 (cytotoxic T lymphocyte associated protein -4), used by the cancer cell to protect itself from the immune system.
Thankfully, because of our understanding, we now have two agents, Nivolumab (Opdivo- Bristol Myers Squibb) and Prembroluzimab (Keytruda – Merck) that interfere with PD-1, as well as Ipilimumab (Yervoy – Bristol Myers Squibb) that interferes with CTLA-4. These drugs are now approved for metastatic melanoma and lung cancer, and are being actively tested in many diseases including, breast, pancreas and ovarian cancer, liver cancer, mesothelioma and colon carcinoma. They have all had dramatic effects on these diseases, but are not without some risk, including over stimulating the immune system to attack healthy organs.
These new agents are the beginning of a new chapter in cancer care, the use of our own immune systemic to control and possibly cure cancer. They are not without their side effects, but this new weapon in the war on cancer will change the way we approach patients and hopefully will bring great benefit to them and their families.
—Dr. Solomon I. Hamburg