Researchers at the Mount Sinai Hospital have developed an mRNA-based treatment for cancer. The approach combines the delivery of mRNA therapy in lipid nanoparticles and also involves co-delivering dendritic cells that have also been primed through treatment with lipid-encased mRNA. The technology aims to overcome some of the immune evasive tricks that tumors use to circumvent the immune system, some of which can hamper more traditional immunotherapies. In contrast, this treatment, which the researchers have called CATCH, aims to progress the cancer immunity cycle by modulating the tumor microenvironment to support an anti-cancer immune response.
Modern immunotherapies can have significant efficacy in various cancers, but they are not always successful. Tumors employ a variety of tricks to disguise themselves from the immune system or suppress its activity in recognizing and destroying cancer cells. One cell type that can be enlisted in the fight against cancer are dendritic cells, which can ‘educate’ T cells on what cells to target. However, treatments targeting dendritic cells have shown mixed success because of the immuno-evasive behavior of tumors.
“Most approaches to boost this critical role of dendritic cells — or adoptive cell therapies — aim to increase the activation signals provided to dendritic cells when specific molecules on their surface bind to tumor cells,” said Yizhou Dong, a researcher involved in the study. “However, these have not been as successful in clinical trials as hoped. This is because tumors have a tendency to evolve in different ways to switch off each stage of the cancer-immunity cycle.”
The CATCH system incorporates a double-pronged attack. One aspect of this includes an mRNA therapy encased in a lipid nanoparticle. The mRNA encodes for CD40, a transmembrane ligand that is present on activated T cells. These nanoparticles lead to the expression of the ligand in cancer cells, which provokes immune-mediated cell death in tumors, which in turn releases loads of tumor antigens into the surrounding area.
The second prong of the attack are dendritic cells that have been removed from a patient, treated using the same mRNA-loaded nanoparticles, and then re-introduced into the patient. These cells react to the increased CD40 expression produced by the first set of nanoparticles in tumor tissue, and go on to reprogram the tumor microenvironment to make it more amenable to further immune attack.
“Dendritic cells have been a key focus for the development of new cancer therapies as these cells organize the cancer-immunity cycle,” said Brian Brown, another researcher involved in the study. “In theory, the CATCH regimen using this particular RNA-based technology has the potential to provide a much more effective approach for using dendritic cells for cancer immunotherapy to treat a wide range of solid tumors.”
Study in journal Nature Nanotechnology: Close the cancer–immunity cycle by integrating lipid nanoparticle–mRNA formulations and dendritic cell therapy
Via: Mount Sinai Hospital