A personalized cancer vaccine developed at Mount Sinai has demonstrated promising results in an early-phase clinical trial, potentially offering a new approach to preventing cancer recurrence in high-risk patients.
Researchers at the Icahn School of Medicine at Mount Sinai have reported positive outcomes from a phase 1 trial of PGV001, a personalized multi-peptide neoantigen cancer vaccine designed to help the immune system recognize and attack cancer cells. The findings, published in the journal Cancer Discovery, show the vaccine generated robust immune responses across multiple cancer types.
Strong Immune Response Across Multiple Cancers
The trial enrolled 13 patients across five different tumor types: non-small cell lung cancer, head and neck cancer, urothelial cancer, breast cancer, and multiple myeloma. All participants had previously received standard treatments but remained at high risk for disease recurrence.
"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. Nina Bhardwaj, Ward-Coleman Chair in Cancer Research and Director of the Vaccine and Cell Therapy Laboratory at Mount Sinai, who led the research.
What distinguishes PGV001 from other cancer vaccines is its use of relatively few antigens compared to recently published trials by other researchers. Despite this, the vaccine successfully induced strong immune responses, suggesting that a carefully selected smaller set of neoantigens may be sufficient for therapeutic effect.
Personalized Approach to Cancer Immunotherapy
PGV001 represents a highly personalized approach to cancer treatment. Using advanced computational tools developed at Mount Sinai, scientists analyze each patient's tumor and germline sequencing data to identify neoantigens—proteins unique to cancer cells that can trigger an immune response.
Unlike tumor-associated antigens found in traditional cancer vaccines, neoantigens are not subject to central tolerance, meaning they can provoke a more robust immune attack against cancer cells. The vaccine is then formulated with peptide sequences encoding these patient-specific neoantigens to optimize immune activation.
"This personalized approach allows us to target the unique mutations present in each patient's cancer," explained Dr. Bhardwaj. "By teaching the immune system to recognize these cancer-specific changes, we aim to provide long-lasting protection against recurrence."
Encouraging Safety and Survival Data
The early results from the trial are encouraging. PGV001 demonstrated a favorable safety profile with no serious side effects reported. At the five-year follow-up mark, six of the 13 treated patients had survived, with three remaining completely tumor-free.
While the small sample size limits definitive conclusions about efficacy, these long-term survival outcomes suggest a potential correlation between the vaccine-induced immune response and improved survival.
Dr. Thomas Marron, a co-investigator on the study, noted, "The fact that we're seeing durable responses in some patients is particularly encouraging given the high-risk nature of the cancers we treated. These early signals warrant further investigation in larger trials."
Addressing Unmet Needs in Cancer Treatment
Over the past decade, immune-based therapies have transformed cancer treatment, including CAR T cells, bi-specific antibodies, antibody-drug conjugates, and immune checkpoint inhibitors. While these approaches have significantly improved outcomes for many patients, some 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 and mount a stronger, targeted response. This approach could potentially complement existing immunotherapies and address current treatment gaps.
Future Directions and Ongoing Research
Based on the promising results from this phase 1 study, Mount Sinai scientists have initiated three additional clinical trials of PGV001:
- A trial in newly diagnosed glioblastoma
- A trial in urothelial cancer combining PGV001 with an immune checkpoint inhibitor
- A trial in prostate cancer
These studies will evaluate the vaccine in larger patient populations and explore potential synergies with other cancer treatments.
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, and Sayali Onkar, PhD. The study received support from the National Cancer Institute of the National Institutes of Health, the Cancer Research Institute, the Parker Institute of Cancer Immunotherapy, and industry partners.
As cancer immunotherapy continues to evolve, personalized vaccines like PGV001 represent a promising frontier in the effort to harness the immune system's power against cancer. While larger studies are needed to confirm these early findings, the approach offers hope for improving long-term outcomes for patients with difficult-to-treat cancers.
