Researchers from Centro Ciencia & Vida observed significant reductions in tumor growth after applying an experimental therapy combining DNA and peptide immunization in preclinical models.

The approach seeks to train the immune system to recognize mutations exclusive to cancer cells, in addition to maximizing the quantity and specificity of immune system cells, explained Dr. Álvaro Lladser.

An experimental study conducted by Chilean scientists demonstrated that a personalized vaccine based on tumor mutations can generate exceptionally high immune responses and therapeutic effects against different types of cancer by combining a DNA-based vaccine with a subsequent peptide boost.

The strategy, evaluated in preclinical laboratory models, successfully achieved robust activation of T cells specific to neoantigens—mutations inherent to cancer cells—and reduced the growth of established tumors, completely eliminating them in approximately 50% of cases.

The results of the work, conducted at Centro Ciencia & Vida of the Fundacion Ciencia & Vida - Universidad San Sebastian (FCV-USS), were published in the scientific journal Oncoimmunology and provide relevant evidence for the development of personalized cancer vaccines, one of the emerging lines of oncological immunotherapy. The article shows that the sequential combination of vaccination platforms can generate more potent immune responses than strategies used in isolation, a central challenge in this field.

“We tested different strategies to create these types of neoantigen vaccines. We found that the combination of two different strategies can create a very robust response. By first immunizing with DNA and then a peptide boost, very high levels of T lymphocytes for these neoantigens can be generated, which can eliminate cancer cells very specifically,” explained Dr. Álvaro Lladser, director of Centro Ciencia & Vida and lead author of the study.

Following the combined vaccination, high levels of tumor-specific T lymphocytes were observed, a key cell type for eliminating cancer cells. In the analyzed models, nearly 20% of all circulating T lymphocytes directly recognized the neoantigens included in the vaccine, suggesting not only robust immune system activation but also the possibility of generating immunological memory and more durable protection against tumor growth.

In addition to measuring the immune response, the study, which also involved researcher Pablo Morgado, evaluated the therapeutic effects of the strategy in various preclinical cancer models, including colorectal cancer, lymphoma, and melanoma. In all cases, reductions in tumor size and the complete elimination of established tumors were observed.

The authors emphasize that these results were obtained in experimental models and that more research is still required before any clinical application; however, they highlight that the data provide consistent evidence on how to optimize the design of personalized cancer vaccines.

How to improve vaccine design

The evaluated strategy is based on so-called neoantigens, mutations that appear in the proteins of cancer cells and differentiate them from healthy cells. Unlike other therapeutic targets, these markers are present only in the tumor, allowing the immune system to distinguish with greater precision which cells to attack. The goal of the vaccine is to “teach” T cells to identify these signals and activate a targeted response against cancer.

“The immune system is designed not to attack its own cells, which is why it sometimes struggles to destroy cancer cells. However, these mutations make the tumor cell different and, therefore, easier to detect and eliminate,” explained Dr. Lladser.

This principle is the basis of personalized vaccines, a line of research that has gained momentum in recent years thanks to advances in genetic sequencing. Identifying the specific mutations of each tumor allows for the design of doses adjusted to each case, with the goal of maximizing the specificity of the immune response and reducing unwanted effects.

“We found that in addition to generating high levels of these T lymphocytes, this immunization strategy can generate memory, which could provide us with long-term protection.”

In addition to immune system activation, the research evaluated the direct impact on established tumors.

In colorectal cancer, lymphoma, and melanoma models, researchers observed significant reductions in tumor growth and complete tumor elimination in approximately 50% of cases. Although the authors emphasize that these results were obtained in experimental models, they highlight that the data provide consistent evidence on how to improve the design of personalized cancer immunizations and enhance their therapeutic effect.

Vaccination order as a key factor

One of the relevant aspects of the experimental work was confirming that not all vaccine combinations generate the same effect, and that the order in which immunization platforms are administered is decisive. The team compared regimens based solely on DNA, solely on peptides, repeated combinations, and reverse sequences, observing substantive differences in the immune response.

The strategy that showed the best results was the initial administration of the DNA-based vaccine, followed later by the peptide boost. This order allowed for higher and more sustained levels of tumor-specific T lymphocyte activation, surpassing the other evaluated alternatives. “Each of these strategies worked well individually, but we found that if we use this precise order, first DNA and then peptide, the response is much higher,” emphasized Dr. Lladser.

Although the researchers have not yet fully identified the biological mechanisms explaining this difference, the results provide a signal for the future design of cancer vaccines. Rather than just adding components, the immunization sequence can define the magnitude and efficacy of the immune response.

Complement to other therapies

The study also explored the potential of this vaccine as a complement to other immunotherapies, particularly immune checkpoint inhibitors (drugs used in cancer immunotherapy that help the immune system activate its defenses against tumor cells). These treatments have transformed the management of several types of cancer, but not all patients respond effectively.

According to the researchers, one reason for this lack of response is the absence of a sufficiently robust prior immune response. In this context, the vaccine could play a key role by generating a base of specific T lymphocytes that can then be enhanced by other therapies.

In this sense, these would be complementary rather than mutually exclusive strategies, according to the director of Centro Ciencia & Vida. “There are many patients who do not respond to anti-PD-1 or anti-CTLA-4 antibodies because they do not present a sufficiently strong immune response, and this vaccine can help generate that initial response.”

This approach opens the possibility of integrating personalized vaccines into combined therapeutic regimens, aiming to improve the overall efficacy of oncological treatment, especially in patients with poorly immunogenic tumors.

The authors caution that the results correspond to an experimental finding made in preclinical models and that further stages of research are still required before evaluating clinical applications in humans. However, they highlight that the main contribution of the work is in the design of more effective vaccines, which platforms to combine, and in what order to apply them to maximize the immune system response.

Various international organizations have highlighted the growing role of immunotherapy in cancer treatment. The World Health Organization (WHO) has noted that these strategies represent one of the most relevant advances of recent decades, allowing for more targeted and potentially more effective treatments than traditional therapies.

Along the same lines, regulatory agencies such as the FDA have approved an increasing number of immunological therapies in recent years, reflecting a paradigm shift in oncology. In this context, research such as that developed by the Chilean team provides key evidence to advance toward more personalized treatments, capable of training the immune system to recognize and attack precisely, an approach that could redefine cancer management in the future.

Text by Luis Francisco Sandoval, Agencia S&M Comunicaciones.