Progress in the fight against malanoma: vaccine slows its progression

In a study carried out by the IrsiCaixa AIDS Research Institute and the Barcelona Supercomputing Center (BSC), a cancer vaccination system was developed that reduces melanoma progression in preclinical studies.

Research published in the journal Journal of Translational Medicineintroduces a new algorithm that improves accuracy when selecting neoantigensmolecules that enable the induction of effective immune responses against cancer for the production of vaccines, IrsiCaixa and BSC said in a joint statement on Tuesday.

Studying

The researchers introduced preclinical melanoma models vaccines prepared according to this algorithm were observed slowing down tumor growthas well as improved survival and they believe VLP vaccination could be a “promising candidate” for future personalized immunotherapy.

As explained by the principal investigator, the research team used vaccines based on virus-like particles (VLP): Nuria Church: “These virus-like particles can be modified a la carte and allow us to administer different combinations of neoantigens, leading to the personalization of these vaccines.”

“The advantage of using VLP compared to other technologies is that we can add approx. 15 different neoantigens and each of them is repeated in about 2500 copies. This allows the body to produce broad immune response against tumor“, added Julia Blancoco-principal investigator of the study and principal investigator of IrsiCaixa.

The human body has the ability to detect the presence of foreign bodies, whether they come from the outside (such as viruses or bacteria) or from the inside (such as cancer cells). To do this, it uses molecules called MHC I, which constantly show protein fragments to the T cells of the immune system. If the proteins represented by MHC-I belong to healthy cells of the body, the body remains normal. On the other hand, if they come from cancer cells, as is the case with neoantigens, T cells activate immune response against themgenerating an antitumor effect.

“When the body detects a foreign molecule, our defenses activate all the emergency alarms. The goal of our research is to find the most immunogenic neoantigen, that is, the one that causes a more powerful immune response,” he clarifies. Carmen Aguilar, co-principal investigator of the study and senior scientist at IrsiCaixa. To do this, it is necessary to find neoantigens that have the greatest affinity for MHC-I and whose structure allows them to bind to MHC-I and contribute to the stimulation of T cells. This will allow the neoantigen to easily bind to MHC-I and for T cells to detect it, causing a good immune response.

“Modern computer algorithms are focused on experimental affinity databases with very low accuracy. With this in mind, we plan to develop a new algorithm: the Neoantigen Optimization Algorithm (NOAH),” he explains. Victor Guallar, co-principal investigator and BSC investigator. “In NOAH, we have added an additional factor based on the structure of the MHC-neoantigen complex and the elemental factors that favor this interaction, resulting in more robust prediction,” he adds.

Encouraging results

The team conducted preclinical experiments using these VLP-based vaccines to which various neoantigens selected by NOAH were added, thus obtaining neoVLP. “Our results are encouraging because we are seeing a slowdown in tumor growth as well as an improvement in survival,” he adds. Ana Barajasco-author of the article and researcher at IrsiCaixa at the time of the study.

In fact, some vaccinated mice did not develop tumors, showing that VLP-induced immune response may be protective. This protective effect may be improved by combination with other therapeutic strategies such as immune checkpoint inhibitors.

Benefits of VLP

VLPs have a number of advantages over other technologies used in vaccine development: firstly, they are safe because they cannot reproduce in the body; secondly, they cause a quick and powerful immune response due to the fact that they resemble viruses in size and structure; and thirdly, finally, in addition to the antigens of interest, VLPs can be loaded with immunomodulators and therefore help induce a more effective immune response.

“Taking into account all these advantages, as well as the results obtained to date, we believe that personalized cancer immunotherapy may consider VLP-based vaccination a promising option for the future,” he concludes. Jorge Carrilloco-principal investigator of the study and principal investigator of IrsiCaixa.