RT Journal Article
SR Electronic
T1 An immune cocktail therapy to realize multiple boosting of the cancer-immunity cycle by combination of drug/gene delivery nanoparticles
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabc7828
DO 10.1126/sciadv.abc7828
VO 6
IS 40
A1 Wu, Jiayan
A1 Chen, Jie
A1 Feng, Yuanji
A1 Zhang, Sijia
A1 Lin, Lin
A1 Guo, Zhaopei
A1 Sun, Pingjie
A1 Xu, Caina
A1 Tian, Huayu
A1 Chen, Xuesi
YR 2020
UL http://advances.sciencemag.org/content/6/40/eabc7828.abstract
AB Immune checkpoint blockade therapy (ICT) has shown potential in the treatment of multiple tumors, but suffers poor response rate in clinic. We found that even combining ICT with chemotherapy, which was wildly used in clinical trials, failed to achieve satisfactory tumor inhibition in the B16F10 model. Thus, we further constructed a previously unexplored immune cocktail therapy and realized multiple boosting of the cancer-immunity cycle. Cocktail therapy consisted of two kinds of tumor microenvironment-responsive drug and gene delivery nanoparticles to achieve specific delivery of doxorubicin and codelivery of plasmids expressed small hairpin RNA of PD-L1 (pshPD-L1) and hyaluronidase (pSpam1) in the tumor area. Experimental evidences proved that any component in the cocktail therapy was indispensable, and the cocktail therapy exhibited excellent antitumor effects against different types of tumors. The cocktail therapy presented here offers a searching strategy for more synergistic units with ICT and is meaningful for developing more efficient antitumor immunotherapy.