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Newswise — All nine patients with in an early-phase trial of a personalized therapeutic vaccine had successful anti-cancer immune responses and remained cancer-free approximately three years after treatment. A therapeutic vaccine is used after disease sets in, aiming to induce immunity to alter the course of disease.

Each patient’s vaccine was created with information found by examining the DNA and RNA in the patient’s tumor, which identified mutations that were only found in the cancer. Like all vaccines, personalized cancer vaccines (PCVs) train the body’s immune system to recognize and destroy a threat. In this case, the threat was any cancer cells remaining after surgery.

The trial was led by Yale Cancer Center (YCC) principal investigator and first author and conducted in close collaboration with colleagues at Dana-Farber Cancer Institute (DFCI). Together, they explored the effectiveness of the PCV specifically for patients with stage III or IV clear cell renal cell carcinoma (ccRCC). The trial’s results will be published in on Feb. 5.

Currently approved immune therapies for kidney cancer aim to “release the brakes” on the immune system to allow it to attack cancer cells, but they do not tell the immune cells where to go. As a result, some patients do not benefit from current therapies, and others may experience side effects from an overactive immune system.

“The idea behind this trial was to specifically steer the immune system toward a target that is unique to the tumor,” said Braun, a researcher in YCC’s Center of Molecular and Cellular Oncology and assistant professor of medicine, pathology, and urology at Yale School of Medicine.

 In the trial, the PCV was designed to find and destroy specific mutated cells that drive tumor growth in patients with ccRCC, which accounts for 80% of all kidney cancer types. Current standard treatment for patients with ccRCC is surgery to remove the cancer, followed by immunotherapy with a targeted therapy.

“For patients with high-risk ccRCC, we want to improve post-surgery treatment options that reduce the risk of the cancer coming back,” said Braun.

In this phase I trial, which is typically performed to assess whether a new treatment is safe or feasible, nine patients received multiple doses of the personalized cancer vaccine. Four patients received just the vaccine and five others also received small doses of the immunotherapy drug ipilimumab.

All nine patients had an immune response within a three-week period and cancer fighting T cells remained elevated for the duration of the study and for years afterward. In seven of nine patients, those T cells were capable of recognizing the patient’s tumor.

“This strong and durable activation in T cells was encouraging and indicates that we're able to generate a long-lasting, anti-cancer immune response with the vaccine,” Braun said.

While patients typically experienced flu-like symptoms for one to two days after their vaccinations, none experienced severe side effects. There were also no significant differences in outcomes between patients who received ipilimumab after vaccination and those who received the vaccine alone.

Vaccines are on the cutting edge of cancer therapy research as a possible treatment option for the future. Successful phase 1 clinical trials, such as this one, typically are followed by successive trials before the results are submitted for approval by the national Food and Drug Administration.

While the results are promising, trials with more patients are needed to confirm the vaccine's effectiveness and explore its full potential. Braun looks forward to the results of an ongoing phase II study (NCT06307431) in which a similar PCV will be administered in combination with the targeted therapy, Keytruda, also known as pembrolizumab. Braun serves on the international scientific advisory committee and is the Yale site principal investigator for this trial. This study involved a large and collaborative team across multiple institutions, with key leadership from co-senior authors Toni Choueiri, Derin Keskin, Patrick Ott, and Catherine Wu from DFCI.

Research reported in this release was supported by the National Institutes of Health under award numbers and . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research was also funded by the Gateway for Cancer Research, U.S. Department of Defense, Louis Goodman and Alfred Gilman Yale Scholar Fund, Yale Cancer Center, Dana-Farber/Harvard Cancer Center, Harvard Medical School, Trust Family Foundation, Michael Brigham, Pan Mass Challenge, Hinda L. and Arthur Marcus Foundation, The Loker Pinard Fund for Kidney Cancer Research at Dana-Farber Cancer Institute, and Conquer Cancer Foundation/Sontag Foundation.

About Yale Cancer Center:

Yale Cancer Center combines a tradition of innovative cancer treatment and quality care for our patients. A National Cancer Institute (NCI) designated comprehensive cancer center since 1974, Yale Cancer Center is one of only 57 such centers in the nation and the only one in Connecticut. Yale Cancer Center members include national and internationally renowned scientists and physicians at Yale School of Medicine and Smilow Cancer Hospital. This partnership enables the Center to provide the best approaches for prevention, detection, diagnosis, and treatment for cancer.