Dendritic cells from induced pluripotent stem cells with an adult phenotype for immunotherapy

Dendritic cells (DCs) offer the potential to be used as potent cancer vaccines. Although DC differentiated from iPS cells offer significant advantages over conventional sources, the derivation of DCs which possess suitable properties has prevented their successful application to date. DCs derived using currently available methods have been shown to display a primitive or ‘fetal’ phenotype, which does not stimulate the immune system effectively, limiting their therapeutic ability.

Oxford researchers have developed a simple solution, which enables the scalable production of DCs that display a mature ‘adult’ phenotype from iPS cells. This methodology provides DCs suitable for application to a variety of indications, including cancer immunotherapy, vaccination against chronic infectious microorganisms, and the induction of tolerance to defined protein antigens. The Oxford invention will greatly facilitate the development of viable Dendritic Cell Therapy.

Dendritic cells

Dendritic cells (DCs) are antigen-presenting cells of the mammalian immune system which directly trigger and control responses by T cells. The use of DCs to prime responses to tumour-associated antigens (TAAs) represents a promising approach to cancer immunotherapy, however, clinically relevant responses have often been disappointing. Although these failures are partly due to the properties of the DCs most commonly used, obtaining sufficient quantities of more suitable DCs has proven difficult.

Foetal phenotypes

Existing methods for obtaining scalable quantities of suitable DCs involve their production from induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs). However, all cell types differentiated from ESCs and iPSCs display a primitive ‘foetal’ or ‘neonatal’ phenotype which may limit their therapeutic utility. DCs derived from iPSCs and ESCs display a similar foetal phenotype which results in limited immunogenicity and increased tolerogenicity.

All grown up

Oxford researchers have developed a simple method of generating DCs which display a mature ‘adult’ phenotype through an exploitation of the epigenetic memory that iPS cells possess for the cell type from which they were derived. DCs derived using this approach combine all the functionality of primary DCs with the many advantages of being derived from a pluripotent source. These advantages include the ability to scale-up procedures, tractability for genome editing and availability of otherwise inaccessible subsets of DCs with desirable properties. DCs displaying an adult phenotype are suitable for applications in a variety of indications, including cancer immunotherapy, vaccination against chronic infectious microorganisms, and the induction of tolerance to defined protein antigens.

Commercialisation

The method, intermediates, and product DCs are the subject of a patent application with scope for international coverage. Oxford University Innovation is seeking external partners to support the commercialisation of the technology.

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