Ludwig Chicago investigator Wenbin Lin and his colleagues reported in Science Advances in October their design and preclinical evaluation of a combined nanotechnology-based radiotherapy strategy that effectively generates a personalized cancer vaccine within the body. It revolves around nanoparticles named nanoscale metal-organic frameworks (nMOFs) developed in Wenbin’s lab that amplify the cell-killing free radicals generated by radiotherapy, boosting its effects. Wenbin’s team adapted their nMOFs to carry an adjuvant, a substance that stimulates vaccine-induced immune responses. The adjuvant, known as a CpG oligonucleotide, drives the maturation of the immune system’s dendritic cells, which activate and direct cytotoxic T cells toward cancer cells. In mouse models of pancreatic and colon tumors, which tend to harbor few viable cytotoxic T cells and so resist immunotherapy, irradiating tumors treated with the nMOFs caused a release of the CpG adjuvant and the shedding of cancer antigens and molecular danger signals by dying cells. This drove dendritic cell maturation and activation, which stimulated anti-tumor T cells and caused regression of treated tumors. When combined with anti-PD-L1 checkpoint blockade immunotherapy, the treatment elicited immune responses against untreated tumors as well—and an 83% cure rate in mice implanted with the immunosuppressive colon cancer.
This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).