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Feasibility, Safety Shown for Personal Tumor Vaccine

Chemotherapy vials

(National Cancer Institute)

5 July 2017. A pilot study among individuals with a form of skin cancer shows a vaccine aiming at proteins specific to a person’s tumor is safe and can generate a complex immune response attacking the tumor. Results of the study, conducted at Dana-Farber Cancer Center in Boston, testing treatments developed by Neon Therapeutics in Cambridge, Massachusetts, appear in today’s issue of the journal Nature (paid subscription required).

Neon Therapeutics is a 2 year-old company founded by researchers at Dana-Farber, MD Anderson Cancer Center in Houston, Washington University in St . Louis, Netherlands Cancer Center,  and the Broad Institute, a medical research center at MIT and Harvard University. The company is developing personalized treatments for cancer that produce immune system reactions addressing neoantigens, peptides — short protein chains — expressed by specific genetic alterations and found on the surface of tumor cells, which can be unique to an individual.

Up to recently, neoantigens were difficult to identify and target, but advances in genomic sequencing and computational biology make it possible to find and capture these peptides in tumors. Neon’s platform takes blood samples from a patient’s tumor and genomically sequences the tumor’s DNA and RNA to find mutations producing the cancer-causing proteins, including neoantigens. The technology uses machine-learning algorithms to predict which neoantigens are most likely to generate strong immune responses. These neoantigens are then isolated and formulated into a vaccine personalized for the patient.

Once injected in the patient, the neoantigens bind to immune system cells that generate T-cells for attacking and destroying the tumor. Each vaccine in the study produced up to 20 different neoantigens, resulting in T-cells attacking multiple targets in the tumor, which reduces the chance the tumor will evade or develop a resistance to the treatments. Neon believes its technology also produces safer cancer treatments that attack only the tumor cells and leave healthy tissue alone.

In this pilot study, 6 patients with melanoma, an advanced and aggressive form of skin cancer, took part whose tumors were already surgically removed, but were still considered at high risk for recurrence. The personalized vaccines were given to the patients at a median of 18 weeks after their surgery. After a median of 25 months, 4 of the 6 patients showed no sign of recurrence in their cancer. In the other 2 participants, however, the cancer spread to their lungs and were treated with pembrolizumab, a checkpoint inhibitor, marketed by Merck under the name Keytruda. The drug successfully treated their secondary tumors, and they remain cancer-free.

The findings confirmed the safety of the treatments, with participants reporting mild side effects including skin irritation at the injection site, fatigue, rash, and flu-like symptoms. As important, the treatments generated a variety of immune responses, attacking the tumors on multiple fronts. Charlotte Wu, the senior author and study leader, says in a Dana-Farber statement, “We are leveraging the immune system’s natural ability to detect and attack many target antigens, as it does every time we get an infection.”

Wu is a researcher at Dana-Farber, the Broad Institute, and Harvard Medical School, as well as a founder of Neon Therapeutics. The company is testing its vaccine, code-named NEO-PV-01, in a clinical trial along with a checkpoint inhibitor like pembrolizumab in patients with metastatic cancer.

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