Development of biological nanoparticles to boost antitumor immunity

Abstract

Immunotherapy approaches have revolutionized perspectives in the treatment of human cancer. Antibodies known as checkpoint inhibitors act on receptors constitutively expressed on lymphocytes, blocking immunosuppressive mechanisms that antagonize the antitumor response. In this way, boosting lymphocyte activity and potentiation of antitumor immune vigilance is stimulated. In recognition of their relevance, immune checkpoint inhibitors were the subject of the 2018 Nobel Prize for medicine. Despite the success of these inhibitors, there are still a number of cases of cancer that are not responsive to existing therapies. In this sense, it is justified the importance of research in this area of knowledge, with the aim of increasing the repertoire of resources available for therapeutics. Our proposal is to develop a new immunotherapy strategy based on the use of biological nanoparticles derived from extracellular vesicles. These vesicles can be multifunctional, decorated with ligands that make it possible to drive the tropism of the particle to the tumor site, stimulate the immune system, and enable the vehiculation of cytotoxic molecules to potentiate the elimination of tumor cells. The rationale for this project is derived from previous findings from our group in which we observed the biological importance of vesicles secreted by antitumor vaccines containing TNFSF receptor ligands. We found that these vesicles had immunomodulatory effects acting on the co-stimulation of T cells. Although these vesicles stimulated T cell activity, this effect was not restricted to the tumor site, since costimulatory particles were administered systemically, without tissue-specific targeting. In this project, we plan to drive the immunomodulatory effect to the tumor site, activating dendritic cells locally and then potentiating the antitumor immune response. (AU)