Immunological incompatibility as a basis for cancer curing and vaccination

In the ULISES project, we aim at developing an immunologic-based treatment strategy where cancer cells are “reprogrammed” to become “visible” to the patient’s own immune system, which will see them as “not belonging to the body” and will attack them, emulating the allogenic response to incompatible transplants. Thus, it will constitute a “natural” treatment, as the patient’s own immune system will be used to attack cancer cells, with no drugs, chemotherapy, radiotherapy, transplants, etc., significantly reducing the treatment time to few weeks and producing minimal or almost null side effects. In addition, this “reprogramming” will lead to an “immunological-memory” avoiding future relapses (vaccine-like effect) through TIL (Tumour Infiltrating Lymphocytes) generated around the tumour microenvironment by the immune system. Porous nanoparticles (NPs) will be used as carriers for delivering a plasmid DNA cargo into the tumour cells in order to produce that “reprogramming”. These NPs will specifically recognize the cancer cells through the CD47 protein and the folate receptors beta and alpha, highly expressed on the surface of the cells. Moreover, two messenger RNAs will be used in order to avoid the side effects caused by targeting CD47 protein (mainly anaemia, neutropenia and thrombocytopenia). Finally, highlight that the ULISES therapeutic strategy will be a “global” treatment, since only with 3 subtypes of NP (one for each chosen alloHLA-A), we will be able to target the entire population for each cancer type. For the implementation and validation of this strategy, we will focus on pancreatic cancer because of its high aggressiveness, lack of effective treatments and little life expectancy, but the developed strategy will also be valid for other cancer varieties with minimal modifications.