Emerging mRNA vaccine strategies target cancer and pathogenic viruses in potent new ways

edited by Stephanie Baum, reviewed by Robert Egan

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The technology that gave the world mRNA COVID vaccines is being tested in a variety of new ways, and emerging research reveals that a crucial T-cell population can be reprogrammed in animal models by reimagining the science that was introduced to the public at the height of the pandemic.

A multidisciplinary team of researchers from departments throughout the University of Pennsylvania is working on two remarkably different methods of using mRNA technology to reprogram cytotoxic T cells—inside the body. These cells are the natural enemies of pathogenic viruses and cancer. The investigators are working on strategies to treat and prevent disease. Their paper is published in the journal Science Immunology.

The T cells under study are known interchangeably as T effector and CD8 T cells. Scientists most frequently refer to them as Teff cells. Results from two University of Pennsylvania studies now show their numbers can be boosted and their killer instincts amplified, similar to the way T cells are supercharged in the cancer treatment known as CAR T-cell therapy. The difference? In the evolving methods, T cells are not removed from the body and supercharged in the lab, then reinfused as in the CAR T-cell immunotherapy technique. Teff cells are boosted in vivo using mRNA technology.

The new research reveals that mRNA technology is versatile and efficient and capable of paving the way to new methods of treating cancer and infectious diseases.

"Selective in vivo reprogramming of cytotoxic effector CD8 T—Teff—cells holds tremendous promise as a therapeutic tool," writes Angela R. Corrigan, lead author of the new research and a member of the large interdisciplinary team at the University of Pennsylvania.

Adoptive cell therapies, such as CAR T-cell immunotherapy, have been developed to treat various cancers, but in addition to the necessity of having to boost patients' T cells in a lab, these therapies are limited by an inability to target Teff cells, scientists asserted in the study.

Corrigan and collaborators overcame this by developing an mRNA and lipid nanoparticle supramolecular complex that homes in on Teff cells bearing a specific biomarker: the fractalkine receptor, CX3CR1.

In mice, the researchers demonstrated that the fractalkine-conjugated mRNA-LNPs targeted up to 95% of blood and splenic Teff cells, a more than formidable army. The study also showed that the targeted T cells could be induced to express specific proteins. The authors further demonstrated that this approach could target and reprogram Teff cells in macaques.

"The ability to reprogram cytotoxic Teff cells in vivo for enhanced immunological function holds notable potential for therapeutic applications across numerous diseases," Corrigan and the team concluded. "Our approach to readily and selectively reprogram only the CD8 T cells with high cytotoxic potential provides a platform for high-precision mRNA-based therapies in which the reprogramming of other T-cell subsets may be unnecessary or unwanted."

Scientists have been exploring multiple ways to boost Teff cells via mRNA-lipid nanoparticle technology. In April 2025, investigators reported on yet another method.

That strategy, which is still in the developmental phase, functions as a lipid nanoparticle vaccine, similar to the COVID immunization, but with the complex capacity to target and reprogram Teff cells. And like the research underway by Corrigan and colleagues, T cells do not have to be removed from a living animal and manipulated in a laboratory.

"Cytotoxic effector CD8 T cells are a critical component of the adaptive immune response given their ability to kill virally infected or cancerous cells," wrote Emily A. Aunins, lead author of a Penn-led 2025 study on an mRNA vaccine that boosts Teff cells through a novel mechanism. That research was also published in Science Immunology.

Messenger RNA technology as it is developed for COVID vaccines produces short-lived immunity, hence the need for frequent booster shots, but Aunins and colleagues developed an mRNA vaccine requiring an adjuvant. The scientists encoded mRNA with the cytokine interleukin-12—IL-12—which amplifies CD8 T-cell responses.

The team found that their lipid-nanoparticle-mRNA vaccine "increased CD8 T-cell responses against SARS-CoV-2 and influenza virus antigens and improved protection against Listeria monocytogenes," Aunins wrote in a summary.

Written for you by our author Delthia Ricks, edited by Stephanie Baum, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

Angela R. Corrigan et al, In vivo reprogramming of cytotoxic effector CD8 T cells via fractalkine-conjugated mRNA-LNPs (2026), Science Immunology. DOI: 10.1126/sciimmunol.aec3436

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