Promising New Trial Using mRNA Vaccine to Prevent Melanoma Recurrence

Connie Franciosi, aged 80, participated in a groundbreaking trial testing an mRNA vaccine combined with an immunotherapy drug to prevent the return of melanoma. Diagnosed in 2020 after spotting a suspicious mark on her skin, Connie’s melanoma was labeled as a late diagnosis—a factor challenging in its management. In the United States, approximately 112,000 cases of melanoma are identified annually, with around 8,500 deaths.

Post-surgery, where Franciosi had her melanoma removed, she faced a high risk of recurrence. Doctors gave her an opportunity to join a clinical trial combining a new messenger RNA (mRNA) vaccine with Keytruda, an immunotherapy drug. This trial involved 157 patients across Australia and the U.S., all post-surgery. Dr. Janice Mehnert of NYU Langone Health, a melanoma specialist and senior author of the recent publication, explains the trial’s unique approach—using mRNA technology to develop a personalized cancer vaccine tailored for each patient’s tumor.

“This is an incredibly interesting trial because the approach is unique,” Mehnert states. “A personalized immunotherapy strategy tailored to each patient’s tumor.”

The results are compelling. After five years, 68.8% of patients receiving the combination treatment remained cancer-free, compared to 49.1% using Keytruda alone—a 49% risk reduction. Additionally, 92% of those on combination therapy survived five years, against 71% on Keytruda.

The American Society of Clinical Oncology conference presents these findings, published in the Journal of Clinical Oncology. Mehnert points out predicting melanoma recurrence is tricky. Sometimes it requires surgery or radiation; at other times, it’s more challenging if spread to lungs or liver. A preventive approach proves advantageous, utilising the immune system early in the disease to improve outcomes.

Dr. Sarah Arron, not involved in the study, supports the results. “This mRNA vaccine is a landmark advance in treating these high-risk melanomas,” she observes. Unlike the COVID-19 mRNA vaccine, used uniformly, this vaccine targets each patient’s unique tumor, boosting the immune system’s response effectively.

Understanding the Combination

Keytruda and the mRNA vaccine collaborate in a sophisticated manner. Immune cells, like T cells, usually identify cancer but can be misled when cancer cells create deceptive ‘don’t attack me’ signals. Keytruda intervenes by removing this shield, awakening T cells to detect the cancer.

Simultaneously, scientists sequence a patient’s tumor, identifying unique neoantigens—up to 34. These are encoded in a tailored vaccine aimed at training T cells to target these neoantigens, providing a detailed blueprint for defeating cancer. Each vaccine corresponds specifically to the patient’s tumor, fine-tuning their immune defense.

Side effects of the trial were minimal, such as chills and mild pain at the injection site. Arron emphasizes understanding this technology, especially after debates surrounding the COVID-19 vaccine. The aim is clear—enhance tumor response, and the prospects for mRNA are “very encouraging.” Researchers are extending investigations into mRNA vaccines with potential in preventing other cancers.

Future Prospects

Dr. David Berman, Moderna’s chief development officer, mentions advancements with intismeran, the developed vaccine, in partnership with Merck, Keytruda’s maker. A Phase 3 trial is already in progress with almost 1,000 participants. Analyzing these new results soon, Moderna aims for FDA approval, signaling hope after many years working on melanoma.

Connie Franciosi exemplifies this hope with her present cancer-free status—a testament to the trial’s impact. Celebrating her 80th birthday, Connie enjoys a fulfilling life, engaging in gardening, library activities, social gatherings, and golfing. As she cherishes life’s simple pleasures, her story stands as a beacon of optimism.