@article{10.1172/jci.insight.98368, author = {Danhong Wang AND Xue F. Huang AND Bangxing Hong AND Xiao-Tong Song AND Liangding Hu AND Min Jiang AND Bin Zhang AND Hongmei Ning AND Yuhang Li AND Chen Xu AND Xiao Lou AND Botao Li AND Zhiyong Yu AND Jiangwei Hu AND Jianlin Chen AND Fan Yang AND Haiyan Gao AND Guoliang Ding AND Lianming Liao AND Lisa Rollins AND Lindsey Jones AND Si-Yi Chen AND Hu Chen}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Efficacy of intracellular immune checkpoint-silenced DC vaccine}, year = {2018}, month = {2}, volume = {3}, url = {https://insight.jci.org/articles/view/98368}, abstract = {BACKGROUND. DC-based tumor vaccines have had limited clinical success thus far. SOCS1, a key inhibitor of inflammatory cytokine signaling, is an immune checkpoint regulator that limits DC immunopotency. METHODS. We generated a genetically modified DC (gmDC) vaccine to perform immunotherapy. The adenovirus (Ad-siSSF) delivers two tumor-associated antigens (TAAs), survivin and MUC1; secretory bacterial flagellin for DC maturation; and an RNA interference moiety to suppress SOCS1. A 2-stage phase I trial was performed for patients with relapsed acute leukemia after allogenic hematopoietic stem cell transplantation: in stage 1, we compared the safety and efficacy between gmDC treatment (23 patients) and standard donor lymphocyte infusion (25 patients); in stage 2, we tested the efficacy of the gmDC vaccine for 12 acute myeloid leukemia (AML) patients with early molecular relapse. RESULTS. gmDCs elicited potent TAA-specific CTL responses in vitro, and the immunostimulatory activity of gmDC vaccination was demonstrated in rhesus monkeys. A stage 1 study established that this combinatory gmDC vaccine is safe in acute leukemia patients and yielded improved survival rate. In stage 2, we observed a complete remission rate of 83% in 12 relapsed AML patients. Overall, no grade 3 or grade 4 graft-versus-host disease incidence was detected in any of the 35 patients enrolled. CONCLUSIONS. This study, with combinatory modifications in DCs, demonstrates the safety and efficacy of SOCS1-silenced DCs in treating relapsed acute leukemia. TRIAL REGISTRATION. ClinicalTrials.gov NCT01956630. FUNDING. National Institute of Health (R01CA90427); the Key New Drug Development and Manufacturing Program of the “Twelfth Five-Year Plan” of China (2011ZX09102-001-29); and Clinical Application Research of Beijing (Z131107002213148).}, number = {3}, doi = {10.1172/jci.insight.98368}, url = {https://doi.org/10.1172/jci.insight.98368}, }