New Hope? The Universal Cancer Vaccine

Written By : Animisha Nekkalapu

Abstract: 

A universal cancer vaccine, once thought to be a dream, may become a reality soon. This is because of the messenger RNA (mRNA) vaccines. Ever since researchers have successfully applied messenger RNA (mRNA) vaccines to prevent Covid-19, they have been seeking a way to develop mRNA vaccines for clinical use. The mRNA cancer vaccines have emerged as a promising novel approach to cancer immunotherapy. They offer high specificity, better efficacy, and fewer side effects compared to traditional treatments. Multiple therapeutic mRNA cancer vaccines are being evaluated in preclinical and clinical trials, with promising early-phase results. However, the development of these vaccines faces various challenges, including tumor heterogeneity, an immunosuppressive tumor microenvironment, and practical obstacles such as vaccine administration methods and evaluation systems for clinical application.

Introduction

Cancer is a large group of diseases that can start in almost any organ or tissue of the body, where abnormal cells grow uncontrollably. They go beyond their usual boundaries to invade adjoining parts of the body, and/or spread to other organs. The latter process is called metastasizing (metastasis) and is a major cause of death from cancer. Cancer is a significant global health challenge. Each year, the American Cancer Society estimates the number of new cancer cases and deaths in the United States. In 2025, 2,041,910 new cancer cases and 618,120 cancer deaths are projected to occur in the United States. Despite these advancements in detection and treatment, many cancers remain difficult to cure, particularly in advanced stages. So cancer continues to be a major public health problem worldwide and requires new strategies and treatment modalities to optimize patient outcomes.

 In this paper, we will mainly discuss universal vaccines in cancer therapy. Therapeutic cancer vaccines aim to stimulate an anti-tumor immune response; a universal cancer vaccine is a therapeutic vaccine designed to target antigens that are widely shared across many tumors and many patients (rather than being individualized for each patient). Universal vaccines promise “off-the-shelf” applicability and the possibility of producing durable, broadly relevant T cell responses that can be combined with other immunotherapies.

Backstory of Cancer Vaccines 

The concept of cancer vaccination and immune-based tumor control dates back to the late 19th century. By the mid-20th century, cancer immunology had begun to take shape through foundational discoveries in immune mechanisms and tumor biology. A pivotal technical milestone for nucleic-acid-based vaccine approaches occurred in 1990, when Jon A. Wolff and his colleagues published a seminal study demonstrating that mRNA could be directly injected into mouse muscle and lead to protein expression in vivo (Wolff et al., “Direct Gene Transfer into Mouse Muscle in Vivo”). That work established the feasibility of using mRNA for gene transfer and protein production in living animals. However, early translation of mRNA approaches into practical vaccines and therapeutics was hindered by mRNA instability and challenges in large-scale manufacturing. These major hurdles slowed progress for many years.

The COVID-19 pandemic (2020–2022) dramatically accelerated the manufacturing and distribution of large-scale mRNA vaccines, proving the platform’s real-world feasibility. This acceleration helped convert mRNA technology from an experimental research platform into a practical modality for clinical use and opened a pathway to apply mRNA vaccines to oncology. The pandemic-era expansion of mRNA capacity catalyzed dozens of clinical trials for cancer vaccines and helped crystallize the concept of universal cancer vaccines around mid-2020 as researchers began to adapt mRNA and other vaccine platforms for shared tumor antigens.

A concrete example of the universal-vaccine concept emerging in this era is UV1 from Ultimovacs (Norway). On December 10, 2020, Ultimovacs announced positive five-year overall survival (OS) data from a Phase I trial evaluating the company’s universal cancer vaccine UV1 in combination with the checkpoint inhibitor ipilimumab in patients with metastatic malignant melanoma. UV1 is a peptide-based vaccine that induces a specific T-cell response against the universal cancer antigen telomerase (hTERT). UV1 is being developed as a therapeutic cancer vaccine platform intended for use in combination with other immunotherapies that require an ongoing T-cell response for their mode of action. To date, UV1 has been tested in four Phase I clinical trials in a total of 82 patients and has maintained a positive safety and tolerability profile as well as shown encouraging signals of efficacy. The promising long-term safety, immune-response data, and early survival signals from these early studies have supported further development of UV1 in larger randomized trials and combinations with checkpoint inhibitors and other immunomodulatory agents.

More broadly, mRNA cancer vaccines have emerged as a promising novel approach to cancer immunotherapy. Ever since researchers successfully applied mRNA vaccines to prevent COVID-19, investigators have been actively seeking ways to develop mRNA vaccines for clinical use in oncology. mRNA cancer vaccines offer several potential advantages over traditional treatments: antigenic specificity, the ability to encode multiple antigens, rapid and scalable manufacturing, and the potential for fewer off-target side effects. Multiple therapeutic mRNA cancer vaccines are now being evaluated in preclinical and clinical trials, with promising early-phase results. Nevertheless, the development of these vaccines faces a number of scientific and practical challenges, including tumor heterogeneity, an immunosuppressive tumor microenvironment, and practical obstacles such as vaccine administration methods and evaluation systems for clinical application. Addressing these challenges will be critical to translating the promise of universal and mRNA-based cancer vaccines into durable clinical benefits.

Recent Breakthroughs

In addition to earlier examples such as UV1, more recent studies highlight the accelerating progress toward a universal cancer vaccine. On July 18, 2025, researchers from the University of Florida (UF) reported findings that may lead to the development of a universal shot capable of jumpstarting the immune system to fight cancer. The study, published in Nature Biomedical Engineering, demonstrated that an experimental mRNA vaccine boosted the tumor-fighting effects of immune checkpoint inhibitors in mouse models.

This work builds upon a breakthrough from the previous year by Sayour’s laboratory. In a first-ever human clinical trial, his team showed that an mRNA vaccine could reprogram the immune system to attack glioblastoma, an aggressive brain tumor with a notoriously poor prognosis. In the four-patient trial, the vaccine was created as a personalized therapy using each patient’s tumor cells, which produced a remarkably rapid and vigorous immune response capable of rejecting the tumor.

In their latest research, Sayour’s team adapted this technology to design a “generalized” mRNA vaccine, meaning it was not tailored to a specific tumor mutation or virus. Instead, it was engineered simply to stimulate a strong, large immune system response. The vaccine’s formulation was produced like COVID-19 mRNA vaccines, though instead of targeting the spike protein of SARS-CoV-2, it was optimized to provoke immune activation against cancer.

The UF researchers observed promising results in melanoma mouse models, particularly in tumors that typically resist treatment. When combined with a PD-1 inhibitor, a type of immune checkpoint inhibitor that trains the immune system to recognize tumors as foreign, the mRNA vaccine substantially improved anti-tumor responses. Even more striking, when tested in mouse models of skin, bone, and brain cancers, an alternative mRNA formulation used as a solo treatment also showed benefit. In some cases, tumors were eliminated entirely.

Mechanistically, the team observed that activating immune responses seemingly unrelated to cancer could revive dormant or “non-functional” T cells, prompting them to multiply and directly kill tumor cells, provided that the immune stimulation was strong enough. This suggests that a generalized immune boost can wake up the body’s natural defenses against tumors, even in contexts where they had previously failed.

The implications of this work are profound. Dr. Elias Sayour, professor in UF’s Lillian S. Wells Department of Neurosurgery and the Department of Pediatrics, emphasized the potential synergy between a generalized mRNA vaccine and existing checkpoint inhibitor therapies. Dr. Duane Mitchell, director of the UF Clinical and Translational Science Institute and co-director of UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy, described the approach as potentially “a universal way of waking up a patient’s own immune response to cancer.” He noted that, if generalizable to humans, this could represent a transformative advance for oncology.

The UF team is now working to optimize current mRNA vaccine formulations and transition into human clinical trials as rapidly as possible. These findings suggest that universal mRNA vaccines may one day serve as both standalone therapies and as powerful partners to immune checkpoint inhibitors, with the capacity to generate broad, durable, and effective anti-tumor immunity.

How the vaccine works

The mRNA cancer vaccine works by instructing the body to produce specific proteins that stimulate immune activity, including Programmed Death-Ligand 1 (PD-L1), a protein often found on the surface or inside cancer cells. Normally, tumor cells exploit PD-L1 to hide from immune system attacks by preventing T cells from recognizing and killing them. However, the vaccine flips this mechanism: by boosting PD-L1 levels, tumors become more vulnerable to immune checkpoint inhibitors that block the PD-1/PD-L1 interaction. This allows the immune system to recognize tumors as foreign and launch a stronger attack against them.

In experimental models, combining the mRNA vaccine with a monoclonal antibody PD-1 inhibitor showed highly promising effects on normally treatment-resistant skin cancers. The antibody acts by signaling to the immune system that the tumor is not “self” and should be destroyed, while the vaccine primes the immune system for an even stronger response.

The vaccine also showed positive results as a solo treatment when tested in mouse models of skin, bone, and brain cancers. In some cases, tumors were eliminated. As senior author Dr. Elias Sayour, a UF Health pediatric oncologist, noted: “This paper describes a very unexpected and exciting observation: that even a vaccine not specific to any particular tumor or virus – so long as it is an mRNA vaccine – could lead to tumor-specific effects.”

Overall, the experimental vaccine successfully reprogrammed immune responses by stimulating PD-L1 expression inside tumors, effectively reawakening T cells that had previously failed to fight cancer. When combined with checkpoint inhibitors, the results were especially striking, showing a new pathway toward developing broad-acting cancer therapies

Conclusion

Despite these advances, significant challenges remain, including tumor heterogeneity, the immunosuppressive tumor microenvironment, and practical barriers to clinical translation. Addressing these obstacles will be critical for realizing the full potential of universal cancer vaccines. If successful, these vaccines could transform cancer care by offering scalable, large, effective therapies that complement and strengthen existing treatment strategies. Continued research, innovation, and clinical testing are essential steps toward making what was once a dream (a universal cancer vaccine) a reality.