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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
Oncolytic Adenovirus Complexes Coated with Lipids and Calcium Phosphate for Cancer Gene Therapy
Jianhua Chen1, Pei Gao1, Sujing Yuan2
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032, China.
Abstract:
Oncolytic adenovirus (OncoAd) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of OncoAd is hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-OncoAd (PLC-OncoAd) delivery system for ZD55-IL-24, an oncolytic adenovirus that carries the IL-24 gene. The negatively charged PLC-ZD55-IL-24 were disperse and resisted serum-induced aggregation. Compared to naked ZD55-IL-24, the systemic administration of PLC-ZD55-IL-24 in BALB/c mice resulted in reduced liver sequestration and systemic toxicity and evaded the innate immune response. In addition, masking the surface of OncoAd protected it from neutralization by pre-existing neutralizing antibody. PLC-OncoAd achieved efficient targeted delivery in Huh-7-bearing nude mice, and intravenous administration of a high dose of PLC-ZD55-IL-24 increased therapeutic efficacy without inducing toxicity. The developed PLC-OncoAd delivery system represents a promising improvement for oncolytic adenovirus-based cancer gene therapy in vivo.
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