Innovative cancer vaccination system slows progression of melanoma
A study published in the Journal of Translational Medicine and carried out by the IrsiCaixa AIDS Research Institute – a center jointly supported by the La Caixa Foundation and the Department of Health of the Generalitat of Catalonia – and the Supercomputing Center of Barcelona – National Supercomputing Centre. (BSC-CNS) created an optimized computer algorithm for selecting highly immunogenic neoantigens.
The research team used this new algorithm in preclinical melanoma models to develop virus-like particle (VLP) vaccines and were able to observe slower tumor progression as well as better survival.
“The advantage of using VLPs over other technologies is that we can add about 15 different neoantigens to each particle, each repeated in about 2,500 copies. This helps the body mount a broad immune response against the tumor,” says Julia Blanco, co-leader 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 outside (such as viruses or bacteria) or from within (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 an immune response against them, generating an antitumor effect.
“When the body detects a foreign molecule, our defenses activate all the emergency alarms. The goal of our study is to find the most immunogenic neoantigen, that is, the one that causes a more powerful immune response,” explains Carmen Aguilar, co-leader 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 target experimental affinity databases with very low accuracy. Given this, we are considering the development of a new algorithm: the Neoantigen Optimization Algorithm (NOAH),” explains Victor Guallar, co-principal investigator of the study and a postdoctoral fellow at the BSC. “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.
Prediction tools allow us to know which molecules activate the immune system. Once identified, it is necessary to find a way to administer them to all patients. IrsiCaixa has a vaccine platform based on VLP, a technology patented by the same institution that it began introducing to fight HIV and which has also become very useful in the fight against cancer. “These virus-like particles can be customized and allow us to administer different combinations of neoantigens, leading to the personalization of these vaccines. This on-demand modification allows us to broaden the target and target different types of cancer using the same platform. In fact, at IrsiCaixa we are currently also working with other types of cancer, including triple negative breast cancer, head and neck cancer and pancreatic cancer,” explains Nuria de la Iglesia, Chief Scientific Officer and Head of Research at IrsiCaixa. cancer in IrsiCaixa.
The research team conducted preclinical experiments using these VLP-based vaccines to which various neoantigens selected by NOAH were added, thereby obtaining neoVLP. “Our results are encouraging because we see a slowdown in tumor growth as well as an improvement in survival,” adds Ana Barajas, co-author of the paper and a researcher at IrsiCaixa at the time of the study. In fact, some vaccinated mice did not develop tumors, indicating that the VLP-induced immune response may be protective. This protective effect may be improved by combination with other therapeutic strategies such as immune checkpoint inhibitors.
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 third, in addition to antigens of interest, VLPs can be loaded with immunomodulators and therefore help induce a more effective immune response. “Taking into account all these benefits, as well as the results obtained so far, we believe that personalized cancer immunotherapy may make VLP-based vaccination a promising option for the future,” concludes Jorge Carrillo, study co-principal investigator and investigator. director of IrsiCaixa.