New topical immunotherapy effective against early skin cancer

November 21, 2016

A combination of two topical drugs that have been in use for years triggers a robust immune response against precancerous skin lesions, according to a new study. The research, from Washington University School of Medicine in St. Louis and Harvard Medical School, shows that the therapy activates the immune system's T cells, which then attack the abnormal skin cells.

The study, which involved patients with actinic keratosis, a precursor to a type of skin cancer called squamous cell carcinoma, is published Nov. 21 in The Journal of Clinical Investigation.

"We looked at precancerous lesions on patients with sun-damaged skin," said Washington University dermatologist and study co-author Lynn A. Cornelius, MD, director of the Division of Dermatology. "Most commonly found on the face, scalp and arms, these lesions appear abnormal by visual examination and under the microscope but are not full-blown skin cancers. But because these lesions have the potential to develop into a true skin cancer, they are commonly treated. Our study shows this combination therapy is more effective and better tolerated than current treatment practices."

On average, the investigational therapy reduced the number of precancerous skin lesions on the face by almost 88 percent compared with a 26 percent reduction using the standard chemotherapy. While some side effects such as skin scaling and itching were similar with both treatments, patients receiving the investigational therapy reported more redness and increased burning sensations, which are consistent with the immune response it triggers. Interestingly, although not specifically measured, patients who had been treated previously with conventional therapies reported decreased pain and discomfort with the combination treatment, according to Cornelius, who is also the Winfred A. and Emma R. Showman Professor of Dermatology.

The investigational treatment combines a cream formulation of a chemotherapy drug called 5-fluorouracil with a synthetic form of vitamin D called calcipotriol. Topical 5-fluorouracil alone is prescribed to treat actinic keratosis. Calcipotriol is approved by the Food and Drug Administration (FDA) for treatment of psoriasis, an autoimmune disorder characterized by red, scaly patches of skin.

Past studies of mice prone to allergic inflammation, especially eczema rash on the skin, have shown that they also are resistant to developing skin cancer. These observations suggested that overreactive immunity triggered by damaged skin may have a beneficial side effect -- a hyper-vigilant immune system that also attacks any cancerous cells that may form. Earlier work at Washington University by senior author Shadmehr Demehri, MD, PhD, now at Harvard Medical School, showed that a protein called TSLP in the skin activates the immune system's T cells, which then attack tumor cells. Calcipotriol also was known to cause the skin to produce TSLP.

"The idea behind this study was to induce a heightened immune response in the skin using calcipotriol combined with the 5-fluorouracil that works to destroy the precancerous cells," Cornelius said. "In so doing, the destroyed precancerous cells release cell proteins, or antigens, and facilitate the heightened immune system to respond. We compared the two-drug formulation to 5-fluorouracil alone over a shorter application period -- four days as opposed to two to four weeks that is typical for the standard treatment of 5-fluorouracil alone."

The current study involved 132 patients with actinic keratosis treated at Washington University School of Medicine in St. Louis. Sixty-five of these patients were randomly assigned to receive the investigational drug combination of 5-fluorouracil plus calcipotriol. The remaining 67 served as a control group and received the standard 5-fluorouracil plus Vaseline petroleum jelly. Patients applied the assigned cream twice daily for four days.

Patients in the investigational and control groups began the trial with similar numbers of precancerous lesions on each part of the body examined. At each body site evaluated, there were on average about 15 lesions on the face, 22 lesions on the scalp, 14 lesions on the right arm and 12 on the left arm. Following treatment, facial lesions were reduced by 88 percent in the investigational group versus 26 percent in the control group. On the scalp, lesions were reduced by 76 percent in the investigational group compared with about 6 percent for the control group. On the right arm, the reduction was 69 percent for the investigational treatment versus about 10 percent for the control. On the left arm, the precancerous lesions were reduced by 79 percent for the investigational treatment compared with 16 percent for the control.

"Because calcipotriol has been shown to induce an immune response, we are now interested in seeing if the anti-tumor immunity of the activated T cells can be recalled later to help prevent both precancerous and cancerous skin lesions," Cornelius said. "We are now planning to re-contact our patients to determine whether there are differences in precancerous and skin cancer rates between the two treatment groups."
-end-
This work was supported by the Washington University Division of Dermatology; the American Skin Association; the Dermatology Foundation; the Burroughs Wellcome Fund; the American Philosophical Society; the La Roche-Posay Research Foundation; and the National Institutes of Health (NIH), grant numbers 1DP5OD021353 and R01GM055479.

Cunningham TJ, Tabacchi M, Eliane JP, Tuchayi SM, Manivasagam S, Mirzaalian H, Turkoz A, Kopan R, Schaffer A, Saavedre AP, Wallendorf M, Cornelius LA, Demehri S. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. The Journal of Clinical Investigation. Nov. 21, 2016.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.