Miriam Merad, MD, PhD, Oncologist and Director of the Precision Immunology Institute at Mount Sinai in New-York is an expert of tissue-resident immune cells in cancer. Here, she discusses how the reprogrammation of these cells (macrophages, dendritic cells, …) could be used as a therapeutic modality in immuno-oncology.
Transcript:
Gene editing in the context of immune resident cells, like to promote one type of macrophage that is more immuno-modulatory versus one that would be more recruiting, do you see something relevant here ? Absolutely, this is a big focus of the group here, the reprogramming of macrophage and dendritic cells in the tumor lesions. So in the tumor microenvironment if we go back to cancer for a minute which is really the main focus of my lab, we also study inflammatory diseases but is to harness this macrophage and dendritic cells and make them more immunogenic. And for us, the way to do that is not to transfer more cells but to go directly and to edit them locally. We could also transfer some groups are doing it, we don’t do that. We just want to try to reprogram them. So you can reprogram them by blocking some checkpoint molecule, this is what James Allison and Tasuku Honjo discovered for T cells, where they block, you know, one checkpoint and they make them more active. Or you can edit them, so you can instead of just blocking one molecule, you can enforce the expression of a group of molecules, using, you know, different types of technology. You have heard of these mRNA vaccines, the sucess of mRNA vaccines has really energized the field of nanoparticle delivery. You know what’s very interesting about macrophages and dendritic cells is that they can eat very well, they can eat even very large particles. All cells can eat. You know, some can take up cellular compartments. But here, the uniqueness of a group of cells which are called phagocytes – macrophages and dendritic cells are part of this phagocyte group, neutrophils is another phagocyte cellular compartment – they can eat very large particles. So if you can play on this, what you can do is deliver, let’s say nanoparticles of big size, that contain different types of mRNA instructions. And here you can somehow redirect or reprogram dendritic cells and macrophages that have been shut down by tumor metabolites for example, or tumor cues. And this is quite exciting, many of us are looking into this.