Cancer immunotherapy has been gained much attention as an alternative treatment for conventional cancer treatments because of its selectivity and less adverse effect. For induction of cancer-specific immune responses, delivery of cancer antigen into antigen presenting cells (APC) such as macrophages or dendritic cells is crucial. Furthermore, the control of intracellular fate of antigen inside of APC is important for induction of cell-based immunity (cellular immunity) or antibody-based immunity (humoral immunity). To eliminate cancer burden, cellular immunity plays a crucial role, which directly kill antigen-expressing tumor cells. For induction of cellular immunity, antigen should be introduced to cytosol of APC by escaping from endo/lysosomal degradation.<br/>We previously developed pH-sensitive polymer-modified liposomes for cytoplasmic delivery of antigen. These liposomes delivered model antigenic proteins into APC and induced antigen-specific cellular immunity in vivo. To improve the immunity-inducing effect of these liposomes, in this study, mannose residue was introduced to pH-sensitive polymer. APC has a mannose receptor on their surface to recognize mannose residue selectively. Therefore, introduction of mannose to pH-sensitive polymer is expected to increase cellular association of liposomes by APC after subcutaneous administration. Furthermore, curdlan, one of beta-glucans derived from cell wall of bacteria, was used as a backbone of pH-responsive polymer having immunity-activating function. Here, synthesis of mannose-introduced pH-sensitive curdlan derivatives, characterization of polymer-modified liposomes and interaction of these liposomes with APC were examined.

Mannose residue-introduced pH-sensitive curdlan-modified liposome for antigen presenting cell-specific antigen delivery system

255th National Meeting (2018)

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