A novel source of rare dendritic cells for immunotherapy

A novel source of rare dendritic cells for immunotherapy

Dendritic cells (DCs) are key players in our immune response. A subset, called CD141+ DCs, are particularly effective in presenting tumour fragments that prime other immune cells against cancer. This makes them attractive immunotherapy candidates. Unfortunately, this subset is incredibly rare, making it impossible to harvest from patients in significant numbers. Induced pluripotent stem cells (iPSCs) offer a possible solution; they have the potential to differentiate into any somatic cell type, allowing production of a large CD141+ DC supply. However, DCs produced this way resemble foetal cells with underdeveloped immunogenicity.

Paul Fairchild’s lab tackled this arrested development by taking advantage of iPSCs’ ‘epigenetic memory’ – DNA modifications which can be retained over generations. In a departure from the standard protocol of generating iPSCs from fibroblasts, they forced common DCs into a stem cell-like state by driving transient expression of stem cell factors. The iPSCs produced were then induced to form rare DCs effective against cancers. The idea was that these iPSCs would retain expression of certain DC genes, aiding development of the rare DCs. Indeed, they demonstrated that the derived DCs resembled adult cells, with strong immunogenicity. By harnessing these cells and forcing them to present tumour fragments of choice, cancer patients could be vaccinated against their disease to enhance their immune response.

Laura Hankins

Horton C, Davies T J, Lahiri P, Sachamitr P, Fairchild PJ (2019).