Re-routing IgE for cancer therapy

Subjects

In healthy immunity, initial allergen exposure induces B cells to produce allergen-specific IgE, which then binds to mast cells (MCs) and sensitizes them to the allergen. After re-exposure, crosslinking of IgE on MCs to the allergen induces MC degranulation and subsequent inflammation. Utilizing this concept to exploit tumour antigens as surrogate allergens, Xu et al. engineered tumour-antigen-specific MCs loaded with an oncolytic virus, to activate MCs and induce tumour cell killing while enhancing local anti-tumour immunity.

Next, to establish IgE-MCs as a drug delivery platform, the authors loaded them with an oncolytic adenovirus (OV). After confirming that OVs were released from OV-containing IgE-MCs (OV@IgE-MCs) in an antigen-specific manner, they showed that neutralizing antibodies targeting the viral-uptake receptor decreased viral delivery only in mice treated with free OV or OV@MCs. Additionally, inhibition of MC degranulation reduced cellular OV uptake from OV@IgE-MCs, together suggesting that the OV enters the melanoma cell via degranulation of the OV@IgE-MCs.

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