Nir Hacohen, PhD
Director of the Center for Cancer Immunology at Massachusetts General Hospital
Krantz Family Center for Cancer Research
A powerful new approach to cancer treatment—designing vaccines for individual patients based on their unique tumor mutations—was pionered by Cathy Wu, MD, Chief of the Division of Stem Cell Transplantation and Cellular Therapies and Lavine Family Chair for Preventative Cancer Therapies at the Dana-Farber Cancer Institute. While earlier forms of cancer vaccines targeted common features shared by many tumors, Wu’s method focuses on neoantigens, which are genetic changes found only in a patient’s specific cancer. She collaborated with colleagues from Dana-Farber and the Broad Institute to combine tumor sequencing, computer modeling, and lab-made peptides to turn these hidden mutations into targets the immune system can recognize and attack. Their discovery led to the launch of Neon Therapeutics, a startup created to bring the technology to patients, and was later acquired by BioNTech, a German biotechnology firm best known for its COVID-19 vaccine, where the technology is currently advancing through clinical trials.
Threading together multiple approaches in one platform
Wu points out that the genesis of this innovation emerged from her experiences in both stem cell transplantation and cancer immunology. She remembers early conversations looking at the “genetic differences between donors and recipients in transplants” and how those differences sparked an immune response. These ideas, combined with the advent of next-generation sequencing led her to ask: “What if we could find the exact mutations in a patient’s tumor that might be immunogenic, synthesize them, and train the immune system to attack?” When sequencing came into existence, she and her colleagues started to think more deeply about how to answer this question. This ultimately led her to thread together sequencing, prediction, and vaccination into one cohesive platform—an innovation she calls “threading the needle”—and bring it into the clinical realm at Dana-Farber.
“A key challenge in this area is to rapidly identify the best targets in each person’s tumor for inclusion in the personalized vaccine. Over many years and continuing today, we develop new experimental and computational methods that allow us to start from DNA and RNA sequences from an individual’s tumor and predict the antigens that are presented on the surface of the tumor, thus marking the tumor for vaccine design,” points out Nir Hacochen, PhD, Director of the Center for Cancer Immunology at Massachusetts General Hospital and a Dana-Farber collaborator. He is one of many researchers who contributed to Wu’s efforts.
There are three specific characteristics of Wu’s platform that make it unique, including:
- Individualized Targeting: Unlike prior vaccines that trained immunity against shared cancer antigens, this method custom-designs each vaccine based on a patient’s specific mutations.
- End-to-End Pipeline: Wu’s team created a fully integrated system—tumor biopsy, sequencing, computational analysis, synthetic peptide design, and clinical delivery—where all components are linked and patient-ready.
- Clinical Translation Focus: There is an emphasis on rapid translation from lab to the clinic. “The infrastructure and clinical translation experience at Dana-Farber allowed us to go from bench to bedside, and then to take the insights from the clinic back to the lab to improve on our understanding of how these vaccines work and can be improved upon,” Wu stresses.
Exploring Safety, Efficiency, and Effectiveness
Wu and her team have conducted and published extensive research that has laid the scientific foundation for translating neoantigen-targeted therapy from experimental concept to clinical investigation. For instance, Wu co-authored a review that appeared in Cancer Immunology Research back in 2013 that first proposed the concept that tumor-specific mutations can yield highly specific immune targets, which raised the potential of developing patient-tailored vaccines.
She also served as senior co-author for a landmark study in Nature in 2017 that explored personalized vaccines targeting up to 20 neoantigens in six melanoma patients, demonstrating the safety, feasibility, and promising outcomes of this approach. In 2018, the team published encouraging results of the neoantigen vaccine approach in treating glioblastoma, a devastating form of brain cancer. Wu and her colleagues followed up with an update in Nature Medicine in 2021 on the original cohort of melanoma patients, sharing evidence that the initial, targeted immune response had broadened and continued to provide continued protection.
Support for Personalized Cancer Treatment
Funding for these efforts has come from a number of sources, including the Broad Institute’s Scientific Projects to Accelerate Research and Collaborations (SPARC) program. Additional financial support came from the Blavatnik Family Foundation to help move the concept from the lab into clinical trials. This early investment signaled growing confidence in the therapeutic promise of neoantigen-based immunotherapy and enabled the launch of the first FDA-approved clinical trial of a personalized cancer vaccine in 2013.
“The SPARC funding gave us the runway to test the idea, and the Blavatnik support provided a vote of confidence that helped move us toward patients,” Wu says.
Commercialization and Ongoing Development
The technology was licensed to Neon Therapeutics in 2015 to move it into commercial development. Since then, Neon expanded the platform, building manufacturing capabilities and launching additional clinical trials targeting multiple tumor types. In 2020, Neon Therapeutics was acquired by BioNTech, which is committed to further accelerating the personalized cancer vaccine platform’s development.
For instance, BioNTech has since integrated the neoantigen technology developed at Dana-Farber into its iNeST (individualized neoantigen specific immunotherapy) pipeline, which remains in active clinical development. The company has also launched several trials to evaluate the efficacy of personalized neoantigen vaccines in combination with checkpoint inhibitors, particularly in patients with melanoma, head and neck cancers, and non-small cell lung cancer.
While no therapies have yet received full regulatory approval, Wu points out that clinical data so far is promising and points to a future where cancer treatment could be customized down to the individual genetic fingerprint of a patient’s tumor.
Looking Ahead
Looking to the future, Wu predicts that the technology that originated at Dana-Farber will continue to play a key role in the evolution path toward regulatory approval and broader clinical application of personalized cancer medicines, utilizing each patient’s cancer genome into a blueprint for their own cure.
Team Members
Catherine J. Wu, MD
Chief, Division of Stem Cell Transplantation and Cellular Therapies, Dana-Farber
Professor, Harvard Medical School
