Researchers at the Icahn School of Medicine at Mount Sinai, led by Nina Bhardwaj, MD, PhD, Ward-Coleman Chair in Cancer Research and Director of the Vaccine and Cell Therapy Laboratory, have tested a promising new type of personalized multi-peptide neoantigen cancer vaccine, called PGV001, in a small group of patients. This early study (phase 1 trial) is an important step in finding better ways to help people fight cancer. The vaccine uses multiple peptides (amino acid sequences) to help the body's immune system recognize and attack cancer cells and stop the disease from coming back. The findings are available in the latest issue of Cancer Discovery , a journal of the American Association for Cancer Research.
Over the last decade, immune-based therapies have transformed cancer treatment, including CAR T cells, bi-specific antibodies, antibody-drug conjugates, and immune checkpoint inhibitors (ICI). These approaches have significantly improved outcomes, but some patients do not respond or eventually develop resistance. Personalized cancer vaccines, like PGV001, aim to overcome these challenges by training the immune system to recognize unique cancer mutations, called neoantigens, and mount a stronger, targeted response.
PGV001 can be made to fit each patient's unique cancer. Scientists use advanced tools to find neoantigens—tiny changes in cancer cells—that are not found in healthy cells. The vaccine then teaches the immune system to target these changes, making treatment more personal and precise. Unlike tumor-associated antigens, neoantigens are not subject to central tolerance, meaning they can trigger a robust immune attack against cancer cells.
"We wanted to develop cancer vaccines that can stop cancer from coming back in patients who are at high risk of recurrence. This study shows that making personalized cancer vaccines is possible and safe," said Dr. Bhardwaj. "This is a phase 1 study with a small group of patients (n = 13) with a variety of cancers (non-small cell lung cancer, head and neck cancer, urothelial cancer, breast cancer and multiple myeloma), but it's an exciting step toward using the immune system to help people live cancer-free, longer."
The study included patients who had already received standard cancer treatments but still had a high risk of the disease returning. Using a computational platform developed by Mount Sinai experts, scientists analyzed tumor and germline sequencing data to select the most promising neoantigens for each patient. The vaccine was then formulated with carefully chosen peptide sequences encoding neoantigens to optimize immune activation. Early results show that PGV001 did not cause serious side effects, and at five-year follow-up, of the 13 patients treated, six patients survived, and three of six surviving patients are tumor free. The vaccine also helped the immune system respond to the cancer which means it may help keep the disease from coming back.
Mount Sinai scientists will continue studying PGV001 in larger groups of patients and testing how it works with other cancer treatments. Data from this phase 1 study have prompted three additional PGV001 trials, one in newly diagnosed glioblastoma, one in urothelial cancer in combination with an ICI, and another in prostate cancer.
Multiple researchers from the Icahn School of Medicine at Mount Sinai contributed to this research, including Mansi Saxena, PhD, Thomas Marron, MD, PhD, Philip Friedlander, MD, PhD, Sayali Onkar, PhD, and more. The National Cancer Institute of the National Institutes of Health, the Cancer Research Institute, the Parker Institute of Cancer Immunotherapy, and industry partners supported this study. A list of all contributors and all connections with pharmaceutical and biotech companies are listed in the full research report. [ https://doi.org/10.1158/2159-8290.CD-24-0934 ]
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight- member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City's large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master's degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. Its Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 500 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges. More than 4,500 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
