Recent developments in cancer immunotherapy promise more effective cancer treatments.
by Aparna Vidyasagar
When foreign invaders such as harmful bacteria and viruses attack, our body’s natural defenses are spurred into action. The various components of the immune system ferret out and destroy disease-causing microorganisms. They also kill any of our body’s cells that have been compromised by these same pathogens. In addition to being constantly vigilant to incursions from the outside, the immune system also has the ability to recognize certain anomalies generated within our own bodies. Case in point: tumors.
Tumors are abnormal cells that grow rampantly, and most often form clumps or mounds. Tumors that have the ability to invade their surroundings are malignant or “cancerous.” All of the cells in our body, including tumors, carry tiny ID tags, or “antigens,” on their surfaces. These help special immune cells (called T cells) to distinguish aberrant cells from normal, healthy ones — and then get rid of them.
Despite this ability, in the cat-and- mouse game between tumors and T cells, tumors emerge as the wily victors. They evade the immune system by manipulating immune processes, and ultimately avoid being recognized and killed. For decades, researchers have been looking to unleash the full power of the immune system on cancer; a concept known as immunotherapy.
It’s been a long road to success, but researchers have made advancements in recent years. In 2013, Science, the venerated peer-reviewed journal, proclaimed cancer immunotherapy as the “Breakthrough of the Year.” Immunotherapy treatments are diverse and creative, targeting the immune system in different ways. They can work by making the immune system more efficient at recognizing or killing cancer cells, or by blocking the mechanisms that cancer cells use to avoid the immune system. Existing immunotherapies have generally proven more successful than traditional cancer treatments such as chemotherapy by prolonging survival and increasing the length of time in which a patient remains in remission.
Provenge, a drug used to treat metastatic prostate cancer, was the first FDA-approved success story. According to an article by the American Cancer Society, Provenge is used to treat patients for whom hormone therapy has stopped working (hormone therapy is a common means of treatment for prostate cancer). The drug works by enhancing the ability of T cells to identify the cancerous cells; it also provides personalized treatment. Doctors isolate immune cells called antigen-presenting cells (APCs) from a patient and grow them in culture with a prostate cancer-specific antigen (the “ID tag” present on the cancer cells). These primed APCs are then reintroduced into the patient’s body, where they stimulate the T cells to attack and kill the prostate tumors. This particular treatment has been shown to prolong survival by four months in some cases.
Provenge is a type of cancer immunotherapy known as a “cancer treatment vaccine.” Unlike a traditional vaccine, which is preventative, treatment vaccines are used only when a disease is in progress. The National Cancer Institute cites research which suggests cancer treatment vaccines may be most effective in combination with other types of cancer therapies (such as surgery, chemotherapy and irradiation) and the results of some clinical trials suggest that cancer treatment vaccines may even be able to increase the effectiveness of these therapies. According to the American Cancer Society, researchers are actively studying cancer treatment vaccines for a variety of cancers including breast cancer, brain cancer (neuroblastoma) and lymphoma.
Other cancer immunotherapies have found better success as stand-alone treatments. In 2011, the FDA approved the use of a drug called Yervoy for treating metastatic melanoma or skin cancer. This drug boosts the capabilities of T cells by targeting an antigen found on their surface: CTLA-4. James Allison, the scientist whose team pioneered research of the antigen, describes it as the “brakes that actually stop the immune system.” Treatment with Yervoy blocks CTLA-4, effectively taking the foot off the brake and allowing T cells to proliferate and aggressively attack the melanoma tumors. According to a press release for an award Allison received this year, remission of at least 10 years has been seen in about 22 percent of patients. Immune related side effects such as dermatitis, varying degrees of liver toxicity, or inflammation of the digestive tract (enterocolitis) do occur, but most of the side effects are reversible.
Another treatment, nivolumab, marketed as Opdivo by Bristol-Myers Squibb, is turning out to be an immunotherapy wunderkind. The FDA approved its use for melanoma treatment in December 2014, and against lung cancer in March 2015. The drug effectively blocks the mechanism by which cancer cells evade detection. Patients taking Opdivo for lung cancer survived a little more than three months longer than those on a standard chemotherapy regimen. The treatment was found to have fewer severe side effects than chemotherapy and a higher survival rate. Twice the number of patients survived a year after taking Opdivo than those who had only undergone chemotherapy. More recently, in July of this year, Bristol-Myers Squibb stopped clinical trials for the treatment of kidney cancer (renal cell cancer) early, in light of the drug’s higher success rate in comparison to standard treatment.
Immunotherapy treatments are not without their downsides. For one, they’re expensive. While cancer treatment in general comes with a steep price tag, the costs vary depending on the drug, and immunotherapy treatments appear to sit at the higher end of the spectrum. For example, a full course of Yervoy costs $120,000 (four doses, given every three weeks) and Opdivo (given every two weeks), according to a recent article in Forbes, costs $150,000 on average. These drugs can be used in combination for melanoma treatment, further bumping up the price. Not all patients respond to immunotherapy treatment and the risk of immune-related side effects does exist, which can lead patients to further medication such as steroids.
Still, immunotherapy remains the next frontier in cancer treatments. Their use for various metastatic cancers represents new hope for patients who may have run out of conventional options. In order to improve patient outcomes, researchers are looking at combining different types of immunotherapies or combining them with traditional cancer treatments. Novel immunotherapy treatments are under development and inching into the mainstream. Currently, clinical trials for leukemia immunotherapy are underway. This treatment, known as CAR therapy, genetically engineers a patient’s T cells to target specific cancerous cells. There may be more FDA approvals in the coming years.
Aparna Vidyasagar is a freelance science writer who writes about life-sciences research and health. She lives in Portland, Oregon. Follow her on Twitter.
