A Phase I Study to Evaluate Safety, Feasibility and Immunologic Response of Adoptive T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Metastatic Melanoma

The purpose of this study is to learn if dendritic cell vaccine will increase the effect of tumor infiltrating lymphocytes given with chemotherapy and interleukin-2 in patients with melanoma.

开始日期2013-10-01

申办/合作机构

Karolinska University Hospital

100 项与 Dendritic cells vaccine(Karolinska University Hospital) 相关的临床结果

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100 项与 Dendritic cells vaccine(Karolinska University Hospital) 相关的转化医学

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100 项与 Dendritic cells vaccine(Karolinska University Hospital) 相关的专利（医药）

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项与 Dendritic cells vaccine(Karolinska University Hospital) 相关的文献（医药）

2023-04-01·Biochemical and Biophysical Research Communications

Anti-TNFR2 enhanced the antitumor activity of a new HMGN1/3M-052 stimulated dendritic cell vaccine in a mouse model of colon cancer

Article

作者: Chen, Xin ; Nie, Yujie ; Pan, Runsang ; Zhu, Lan ; Li, Linzhao ; Yang, De ; Wang, Chenglv ; Chen, Shuanghui ; Wang, Mengjiao ; Nie, Yingjie ; Zhang, Xiangyan ; Gui, Huan ; Jing, Qianyu

Immunotherapy is the new approach for cancer treatment that can be achieved through several strategies, one of which is dendritic cells (DCs) vaccine therapy. However, traditional DC vaccination lacks accurate targeting, so DC vaccine preparation needs to be optimized. Immunosuppressive CD4⁺Foxp3⁺ regulatory T cells (Tregs) in the tumor microenvironment can promote tumor immune escape. Therefore, targeting Tregs has become a strategy for tumor immunotherapy. In this study, we found that HMGN1 (N1, a dendritic cell-activating TLR4 agonist) and 3M-052 (a newly synthesized TLR7/8 agonist) synergistically stimulate DCs maturation and increase the production of proinflammatory cytokines TNFα and IL-12. In a colon cancer mice model, vaccination with N1 and 3M-052 stimulated and tumor antigen-loaded DCs combined with anti-TNFR2 inhibited tumor growth in mice, and the antitumor effect was mainly achieved through stimulation of cytotoxic CD8 T cell activation and depletion of Tregs. Overall, the combinating of DC activation by N1 and 3M-052 with inhibition of Tregs by antagonizing TNFR2 as a therapeutic strategy may represent a more effective strategy for cancer treatment.

2021-01-01·Journal of Cancer3区 · 医学

Sequential administration of anti-PD-1 and anti-Tim-3 combined with an SA-GM-CSF-anchored vaccine overcomes adaptive immune resistance to reject established bladder cancer

3区 · 医学

ArticleOA

作者: Li, Jinlong ; Shi, Xiaojun ; Shi, Xianghua ; Long, Zhaolin ; Gao, Jimin ; Liu, Guang ; Zhang, Xinji ; Mo, Lijun ; Tan, Wanlong

Program death receptor-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) play an important role in tumor immune evasion. PD-1 blockade could produce an effective anti-tumor effect but the response rate was low due to lacking of tumor infiltrating lymphocytes (TILs) and existing of other negative regulatory pathways. Streptavidin(SA)-GM-CSF surface-anchored tumor cells vaccine could induce specific anti-tumor immune response. However, this vaccine failed to induce regression of established tumor because it also up-regulated PD-1 expression on tumor cells dependent on IFNγ and up-regulated PD-1/Tim-3 expression on CD8⁺ TILs. Subsets of CD8⁺ TILs assay showed that PD-1 expression was closely associated with CD8⁺ TILs exhaustion, and Tim-3 expression was closely correlated with secretion function but not proliferation of CD8⁺ TILs. Sequential administration of anti-PD-1 and anti-Tim-3 could further improve the efficacy of SA-GM-CSF-anchored vaccine therapy, and tumor regression was noted in over 50%. This triple therapy improves the specific cytotoxic activity and decreased the apoptosis of CD8⁺ TILs. These findings indicated that this triple therapy could induce a more robust anti-tumor immune response.

2017-01-01·Theranostics1区 · 医学

Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice

1区 · 医学

ArticleOA

作者: Zhao, Yongxiang ; Duan, Siliang ; He, Jian ; Lu, Xiaoling ; Zhou, Sufang ; Chen, Jiaojiao ; Su, Jing ; Zhang, Zhiyong ; Hu, Zixi ; Yang, Nuo ; Zhang, Zhenghua

Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-γ responses. Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis. Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.

100 项与 Dendritic cells vaccine(Karolinska University Hospital) 相关的药物交易

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