Researchers at the Icahn School of Medicine at Mount Sinai have achieved a significant milestone in personalized cancer treatment, demonstrating that their custom-made vaccine PGV001, when combined with immune checkpoint inhibitor therapy, safely generates robust immune responses in bladder cancer patients. The phase 1 study results, published in Nature Cancer, were led by Dr. Nina Bhardwaj and Dr. Matthew Galsky.
The trial enrolled 10 patients with bladder cancer who received individualized versions of the PGV001 vaccine alongside atezolizumab (Tecentriq). Each vaccine was specifically designed to target the unique mutations present in the patient's tumor.
"Our findings move the field forward by showing how personalized vaccines like PGV001 can work in bladder cancer," said Dr. Bhardwaj, Ward-Coleman Chair in Cancer Research and Director of Mount Sinai's Vaccine and Cell Therapy Lab. "We've proven these custom vaccines can consistently activate the immune system in powerful, cancer-fighting ways."
How PGV001 Works
The PGV001 vaccine employs advanced tumor sequencing and a computational platform developed at Mount Sinai to identify tumor-specific mutations, known as neoantigens, that are most likely to trigger immune responses. Researchers then create synthetic peptides based on these markers to develop a personalized vaccine.
When administered with immunotherapy drugs like atezolizumab, PGV001 trains the immune system to recognize and attack cancer cells while sparing healthy tissue. This approach represents a significant advancement in precision medicine for cancer treatment.
The study demonstrated that the combination therapy was well-tolerated, with patients experiencing only mild injection-site reactions. Importantly, all participants showed vaccine-specific T cell responses that were not present before treatment.
Addressing an Urgent Need
Bladder cancer responds well to immune-based treatments, but not all patients benefit equally from current approaches. According to the American Cancer Society, approximately 84,870 new cases of bladder cancer and 17,420 deaths are expected in the United States this year.
"This study adds to growing evidence that combining personalized vaccines with immunotherapy could help many more patients benefit," explained Dr. Galsky, Co-Director of the Center of Excellence for Bladder Cancer and Associate Director for Translational Research at The Tisch Cancer Institute. "It also lays the groundwork for larger trials that are now underway."
Expanding Applications
Building on the success of PGV001 in eliciting immune responses across multiple cancer types, the personalized vaccine is now demonstrating encouraging results specifically in bladder cancer. The approach shows particular promise for patients whose tumors are resistant to existing therapies.
The Mount Sinai team is working to accelerate the vaccine's development, expand its accessibility, and test new combinations to help more patients. The individualized approach offers renewed hope, particularly for those who don't respond to standard treatments.
Collaborative Effort
The study represents a collaborative effort at Mount Sinai, bringing together experts in immunology, oncology, genetics, and pathology. Key contributors included Dr. Mansi Saxena, Dr. Jonathan Anker, Dr. Julia Kodysh, and Dr. Anna Kaminska, among others.
The research received support from the National Cancer Institute of the National Institutes of Health, the Cancer Research Institute, the Parker Institute of Cancer Immunotherapy, and various industry partners.
As personalized cancer vaccines continue to generate excitement in the oncology community, this study provides important evidence that such approaches can be safely implemented and may enhance the efficacy of existing immunotherapies. The results support ongoing larger trials that could eventually lead to new treatment options for bladder cancer patients.
