Mannan‐mediated gene delivery for cancer immunotherapy

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Abstract
Summary: Recent years have seen a resurgence in interest in the development of efficient non‐viral delivery systems for DNA vaccines and gene therapy. We have previously used oxidized and reduced mannan as carriers for protein delivery to antigen‐presenting cells by targeting the receptors that bind mannose, resulting in efficient induction of cellular responses. In the present study, oxidized mannan and reduced mannan were used as receptor‐mediated gene transfer ligands for cancer immunotherapy. In vivo studies in C57BL/6 mice showed that injection of DNA encoding ovalbumin (OVA) complexed to oxidized or reduced mannan‐poly‐L‐lysine induced CD8 and CD4 T‐cell responses as well as antibody responses leading to protection of mice from OVA+ tumours. Both oxidized and reduced mannan delivery was superior to DNA alone or DNA‐poly‐L‐lysine. These studies demonstrate the potential of oxidized and reduced mannan for efficient receptor‐mediated gene delivery in vivo, particularly as DNA vaccines for cancer immunotherapy.

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