Adoptive cellular immunotherapy of tumors via effective CpG delivery to dendritic cells using dendrimer-entrapped gold nanoparticles as a gene vector.

Abstract

The major obstacle that hinders current cancer immunotherapies is the development of an effective approach to promote a proper immune response for effective tumor killing through activated T cells. Herein, we report an effective T cell-based tumor immunotherapy approach through nonviral delivery of a cytosine-guanine (CpG) oligonucleotide using dendrimer-entrapped gold nanoparticles (Au DENPs). In our work, Au DENPs partially decorated with methoxy polyethylene glycol (mPEG) were synthesized and characterized to be used as a vector for CpG delivery to bone marrow-derived dendritic cells (BMDCs). The BMDCs matured via CpG delivery were used to activate T cells for adoptive immunotherapy of cancer cells. We show that the developed PEGylated Au DENPs are able to effectively transfect CpG leading to the maturation of BMDCs that can be used to activate T cells for subsequent adoptive immunotherapy of cancer cells in vitro and a xenografted melanoma tumor model in vivo after intravenous injection. Importantly, the developed approach to genetically engineer BMDCs enables a triggered adaptive immune response and memory of T cells, which can be beneficial for effective inhibition of tumor metastasis and recurrence. The developed nonviral gene delivery approach using Au DENPs as a vector for T cell-based immunotherapy can be applied to different cancer types.