Nanovacunas basadas en listeria como inmunoterapia frente a tumores sólidos

Laburpena

Dendritic cell-based (DC-based) vaccines are promising immunotherapies for cancer. However, several factors, such as the lack of efficient targeted delivery and the sources and types of DCs, have limited the efficacy of DCs and their clinical potencial. Solid tumours are among the leading global causes of human mortality. Treatments of solid tumors include, surgery, radiotherapy, chemotherapy and immunotherapy. To avoid relapses and aggressive post-surgery secondary tumors, adjuvant therapy after surgery is recomended. Cancer vaccines are adjuvant therapies avialable for cutaneous melanoma and can be inoculated to elict long-lastic immune responses and control small metastatic foci. However, trials using ex vivo DCs loaded with melanoma peptides benefited only a small number of patiens and led to no improvement in overall survival (OS). For this reason, activating DCs in vivo, has the purpose of stimulating their dual immune action, either in the priming stage as adjuvants or in the effector stage as immunestimulators. Bacterial peptides of listeriolysin O (LLO91-99) a bacterial cytotoxin of Listeria monocytogenes, presented the ability to target to tumours and induce apoptosis, when loaded into DC that cause melanoma regression and benefit OS, being a promising therapy for tumours. Also, nanotecnology has created expectations in the field of cancer immunotherapy, due to their reduce toxicity, improvement of antigen presentation, modulation of innate immunity or the targeting to selected cells and tissues, being promising platforms for synthetic vaccines.In this regard, nanoparticiles act as novel carrieres to improve antigen loading of DCs, and present adjuvant activities. Here, we combine gold glyconanoparticles (GNP), nanomaterials able to incorporate on the same gold nanoplatform, carbohydrates as glucose that target to DCs and bacterial peptides with exceptional anti-tumour abilities as LLO91-99. We based our hypothesis in the efficiency of GNP- LLO91-99 nanovaccines as listeriosis vaccines that induce Th1 immune responses after activating in vivo DCs. We propose GNP-LLO91-99 nanovaccines as novel adjuvants for cancer therapy and a therapeuitc vaccine for cutaneous melanoma, acting as a novel immunotherapy easy to test in human blood samples.