Revolutionary RNA Vaccine Makes Tumors Disappear In Trials

Scientists are developing an RNA vaccine that can "wake up" the immune system and help it recognize and destroy different types of cancer. In animal tests, it even caused resistant tumors to shrink or disappear, especially when combined with drugs already used in immunotherapy. This discovery paves the way for the creation of a possible "universal cancer vaccine" in the future.

Cancer immunotherapy is a rapidly advancing area of ​​medicine, as it seeks to harness the patient's own immune system to fight tumors. Typically, these therapies work best in cancers with many mutations, because these alterations make the tumors more visible to the body's defense cells.

However, many cancers are poorly mutated and therefore difficult for the immune system to recognize, making them resistant to this type of treatment.

Recent research shows that the key to overcoming this resistance may lie in intensely stimulating the immune system, rather than targeting only specific tumor proteins. This could be done through experimental messenger RNA vaccines, a technology similar to that used in some COVID-19 vaccines.

Messenger RNA vaccines are a type of modern immunization that uses a synthetic copy of a molecule called messenger RNA to teach the body how to defend itself. RNA acts as a "recipe" that instructs cells to temporarily produce a specific protein, similar to one found in viruses or diseased cells.

In this case, instead of teaching the body to recognize a specific virus, RNA vaccines teach cells to produce proteins that strongly activate the immune response, as if the body were fighting an infection. This extra stimulus can "awaken" previously dormant defense cells and direct them against the cancer.

This protein, by itself, does not cause disease, but it is enough for the immune system to recognize it as foreign and produce antibodies and defense cells. Thus, if the person is exposed to the real virus or tumor cell in the future, the body will already be prepared to fight it quickly and effectively.

Studies conducted in animal models have shown surprising results. When researchers administered the RNA vaccine along with drugs already used in immunotherapy, called immune checkpoint inhibitors, previously resistant tumors began to shrink. In some cases, the vaccine alone was enough to completely eliminate the tumors.

This effect appears to occur because the vaccine induces an initial response of interferon, a protein normally produced by the body in response to infections. This response creates an environment in which immune cells not only attack the treated tumor but also begin to recognize other parts of the cancer, increasing the immune system's reach and preventing the disease from returning.

This image shows an experiment conducted on mice to test a new RNA cancer vaccine. D, we see that the animals received tumor implants and were then treated weekly with the experimental vaccine. E, the graph shows that the mice treated with the vaccine lived significantly longer than the untreated ones or those given only another type of drug. G, the images compare the animals' lungs: those without treatment appear riddled with tumors, while those treated with the vaccine have much clearer organs, with far fewer signs of the disease. This suggests that the vaccine helped the immune system fight the cancer effectively.

Most interestingly, this strategy does not rely on previously identifying which mutations are present in each patient. This opens the possibility of a "universal cancer vaccine," which could be used broadly to sensitize the immune systems of different people against their own tumors.

Instead of relying solely on traditional treatments such as surgery, chemotherapy, or radiation therapy, this approach could transform dormant defense cells into active cancer killers.

Researchers are now working to refine these vaccines, better understand how to increase their effectiveness, and begin clinical trials in humans. If the promising results in animals are confirmed in people, this could be a decisive step toward changing the way we treat resistant cancers and paving the way for more personalized, safe, and effective therapies.

READ MORE:

Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading

Sadeem Qdaisat, Brandon Wummer, Brian D. Stover, Dingpeng Zhang, James McGuiness, Frances Weidert, Jonathan Chardon-Robles, Adam Grippin, Anna DeVries, Chong Zhao, Christiano Marconi, Aida Karachi, Chao Xie, Gabriel Jobin, Ruixuan Liu, Stephen Michel, Xiaojie Ma, Rachel S. F. Moor, Christina von Roemeling, Duy T. Nguyen, Leighton Elliott, Nagheme Thomas, Arnav Barpujari, Hilary Geffrard, Yodarlynis Campaneria, Elizabeth Ogando-Rivas, Cathleen Rabideau, Dhruvkumar Soni, Jianping Huang, Sheila Carrera-Justiz, Kristianna Fredenburg, Natalie L. Silver, W. Gregory Sawyer, Maryam Rahman, John A. Ligon, Catherine T. Flores, Ji-Hyun Lee, Duane A. Mitchell, Paul Castillo, Hector R. Mendez-Gomez, and Elias J. Sayour

Nature Biomedical Engineering. 18 July 2025.

DOI: 10.1038/s41551-025-01380-1

Abstract: 

The success of cancer immunotherapies is predicated on the targeting of highly expressed neoepitopes, which preferentially favours malignancies with high mutational burden. Here we show that early responses by type-I interferons mediate the success of immune checkpoint inhibitors as well as epitope spreading in poorly immunogenic tumours and that these interferon responses can be enhanced via systemic administration of lipid particles loaded with RNA coding for tumour-unspecific antigens. In mice, the immune responses of tumours sensitive to checkpoint inhibitors were transferable to resistant tumours and resulted in heightened immunity with antigenic spreading that protected the animals from tumour rechallenge. Our findings show that the resistance of tumours to immunotherapy is dictated by the absence of a damage response, which can be restored by boosting early type-I interferon responses to enable epitope spreading and self-amplifying responses in treatment-refractory tumours.