A new comprehensive review from researchers at the Icahn School of Medicine at Mount Sinai details how decades of cancer vaccine research are converging into a new era of more precise, personalized, and effective immunotherapies, particularly when combined with other cancer treatments.
The review, titled "Pipe Dream to Pipeline: Journey of Cancer Vaccines and the Road Ahead" and published in Cell Reports Medicine , examines the evolution of therapeutic cancer vaccines, with a special focus on neoantigen-based vaccines—highly personalized vaccines designed using genetic mutations unique to a patient's tumor.
"Cancer vaccines were once seen as a promising idea that struggled to deliver durable clinical benefit," said Nina Bhardwaj, MD, PhD, senior author of the review, Ward-Coleman Chair in Cancer Research, and Director of the Vaccine and Cell Therapy Laboratory at the Icahn School of Medicine at Mount Sinai, and Co-Director of the Cancer Immunology Program at the Mount Sinai Tisch Cancer Center. "Today, advances in sequencing, immune profiling, and vaccine platforms are transforming that landscape and opening the door to more effective, long-lasting immune responses against cancer."
While early cancer vaccines showed limited success as standalone treatments, the review highlights how modern technologies have revitalized the field. Improvements in tumor sequencing and a deeper understanding of the tumor microenvironment have enabled researchers to identify precise immune targets and design vaccines that better activate cancer-fighting T cells.
Clinical trial data summarized in the review show that personalized neoantigen vaccines (delivered as peptides, DNA, or mRNA) are safe and capable of generating robust immune responses across a range of cancers, including melanoma, pancreatic cancer, glioblastoma, lung cancer, and bladder cancer.
Importantly, the authors note growing evidence that cancer vaccines may be most effective when used in combination with immune checkpoint inhibitors and other standard therapies, helping overcome immune resistance and improve patient outcomes.
The review synthesizes decades of clinical research and identifies key reasons earlier cancer vaccines fell short, including immune suppression within tumors and limitations in antigen selection. It also outlines persistent challenges, such as the time and cost required to manufacture personalized vaccines and the need for better biomarkers to predict response.
At the same time, the authors highlight emerging strategies, such as shared "off-the-shelf" neoantigen vaccines and improved vaccine delivery platforms, that could expand access and accelerate clinical use.
By drawing together insights from past and ongoing clinical trials, the review outlines a road map for integrating cancer vaccines into standard-of-care treatment, particularly in early-stage disease and in combination with other immunotherapies.
The authors emphasize that while most cancer vaccine clinical trials to date have been early-phase studies, larger randomized clinical trials will be critical to defining how these therapies can best improve survival and quality of life for patients.
"Pipe Dream to Pipeline: Journey of Cancer Vaccines and the Road Ahead" was authored by Sayali Onkar, PhD, under the guidance of Dr. Bhardwaj along with investigators Cansu Cimen Bozkus, PhD, and Mansi Saxena, PhD, from the Vaccine and Cell Therapy Laboratory and the Division of Hematology and Oncology at the Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, with collaborators from the Parker Institute for Cancer Immunotherapy.
