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A Chromatin-Mimetic Nanomedicine for Therapeutic Tolerance Induction
journal contribution
posted on 2018-11-09, 00:00 authored by Bowen Li, Zhefan Yuan, Patrick McMullen, Jingyi Xie, Priyesh Jain, Hsiang-Chieh Hung, Shihan Xu, Peng Zhang, Xiaojie Lin, Kan Wu, Shaoyi JiangThe undesirable immune
response poses a life-threatening challenge
to human health. It not only deteriorates the therapeutic performance
of biologic drugs but also contributes to various diseases such as
allergies and autoimmune diseases. Inspired by the role of chromatin
in the maintenance of natural immune tolerance, here we report a DNA-protein
polymeric nanocomplex that can mimic the tolerogenic function of chromatin
and induce an immune tolerance to its protein cargos. We first proved
that the chromatin-mimetic nanomedicine loaded with keyhole limpet
hemocyanin (KLH), a highly immunogenic model protein, could elicit
a durable antigen-specific immune tolerance to KLH lasting for at
least five weeks in mice. Following the proof-of-concept study, we
demonstrated that this nanomedicine could be applied to improve the
safety and efficacy of a biologic drug, PEGylated uricase, by attenuating
the relevant antibody (Ab) responses. Moreover, we also demonstrated
that prophylactic treatments with this nanomedicine could tolerize
the immune system with the allergen of ovalbumin (OVA) and thus inhibit
the occurrence of airway inflammation in an OVA-induced allergic asthma
murine model. Collectively, our work illustrates a nature-inspired
concept of immune tolerance induction and establishes a useful tool
to specifically suppress unwanted immune responses for therapeutic
purposes.
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Chromatin-Mimetic Nanomedicineproof-of-concept studykeyhole limpet hemocyaninprophylactic treatmentsasthma murine modelimmunogenic model proteintolerance inductiontolerogenic functionprotein cargosTherapeutic Tolerance Inductionairway inflammationKLHresponsechromatin-mimetic nanomedicinenature-inspired conceptPEGylated uricaseOVA
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