Induction of Neo-Antigen Specific Cytotoxic T Cells by Autologous Tumor Lysate-loaded Specialized Cross-Presenting Dendritic Cells in Epithelial Ovarian Cancer Patients Treated With Neoadjuvant Chemotherapy, the NEODOC Study

This goal of this single arm, single center, exploratory phase I/II clinical trial is to learn more about the immunological efficacy, safety and feasibility of an autologous tumor lysate-loaded autologous XP-DC (cDC1)-based vaccine in patients with ovarian cancer.

开始日期2023-03-17

申办/合作机构

Radboud University Medical Center

NCT04212377 / Completed临床2期IIT

An Exploratory Study: Dendritic Cells for Immunotherapy of Metastatic Endometrial Cancer Patients

Prevention of infectious diseases through immunization is one of the greatest achievements of modern medicine. Nonetheless, considerable challenges remain for improving the efficacy of existing vaccines for therapeutic immunizations for diseases such as cancer. The investigators were amongst the first groups worldwide that introduced tumor antigen-loaded dendritic cell (DC)-based vaccines in the clinic1-3. Effective immune responses and favorable clinical outcomes have indeed been observed4-7. Thus far, mainly conventional in vitro generated monocyte-derived DCs (moDC) have been used in clinical trials worldwide. In the past 14 years the investigators have treated more than 375 patients and proven that DC therapy is feasible and non-toxic. The investigators observed that long lasting tumor specific T cell-mediated immunological responses are clearly linked to increased progression free survival as well as overall survival8.
In conclusion, based on all these observations the investigators are convinced that pDC and myDC employ different, and probably more optimal mechanisms to combat cancer. In addition, based on in vitro data and preclinical studies that suggest that blood pDC and myDC act synergistically, the investigators hypothesize that the combination of myDC and pDC may induce stronger anti-tumor immune responses as compared to pDC or myDC alone, or moDC.

开始日期2019-04-08

申办/合作机构

Radboud University Medical Center

[+1]

ChiCTR1900021177 / RecruitingIIT

Personalized dendritic cell-based immunotherapy of hepatocellular carcinoma

开始日期2018-10-08

申办/合作机构-

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项与 Dendritic Cells(Radboud University Medical Center) 相关的文献（医药）

2024-05-01·Oral Oncology

Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma – A Systematic Review and Meta-analysis

Review

作者: Lee, Rachel Siying ; Lim, Nicholas E-Kai ; Tan, Ethan ; Lim, Chwee Ming ; Toh, Han Chong ; Jang, Isabelle Jia Hui ; Yeo, Brian Sheng Yep

BACKGROUNDRecurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective.METHODSWe systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias.RESULTSWe screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved.CONCLUSIONCBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.

2020-01-01·American journal of translational research

Prediction of therapeutic outcome and survival in a transgenic mouse model of pancreatic ductal adenocarcinoma treated with dendritic cell vaccination or CDK inhibitor using MRI texture: a feasibility study.

Article

作者: Li, Yu ; Yang, Jia ; Benson Iii, Al B ; Yaghmai, Vahid ; Eresen, Aydin ; Shangguan, Junjie ; Zhang, Zhuoli ; Sun, Chong ; Hu, Su

There is a lack of a well-established approach for assessment of early treatment outcomes for modern therapies for pancreatic ductal adenocarcinoma (PDAC) e.g. dinaciclib or dendritic cell (DC) vaccination. Here, we developed multivariate models using MRI texture features to detect treatment effects following dinaciclib drug or DC vaccine therapy in a transgenic mouse model of PDAC including 21 LSL-Kras^G12D ; LSL-Trp53^R172H ; Pdx-1-Cre (KPC) mice used as untreated control subjects (n=8) or treated with dinaciclib (n=7) or DC vaccine (n=6). Support vector machines (SVM) technique was performed to build a linear classifier with three variables for detection of tumor tissue changes following drug or vaccine treatments. Besides, multivariate regression models were generated with five variables to predict survival behavior and histopathological tumor markers (Fibrosis, CK19, and Ki67). The diagnostic performance was evaluated using accuracy, area under the receiver operating characteristic curve (AUC) and decision curve analyses. The regression models were evaluated with adjusted r-squared (R_adj ²). SVM classifier successfully distinguished changes in tumor tissue with an accuracy of 95.24% and AUC of 0.93. The multivariate models generated with five variables were strongly associated with histopathological tumor markers, fibrosis (R_adj ²=0.82, P<0.001), CK19 (R_adj ²=0.92, P<0.001) and Ki67 (R_adj ²=0.97, P<0.001). Furthermore, the multivariate regression model successfully predicted survival of KPC mice by interpreting tumor characteristics from MRI data (R_adj ²=0.91, P<0.001). The results demonstrated that MRI texture features had great potential to generate diagnosis and prognosis models for monitoring early treatment response following dinaciclib drug or DC vaccine treatment and also predicting histopathological tumor markers and long-term clinical outcomes.

2010-06-01·Journal of Immunotherapy4区 · 医学

Combined Treatment With Dendritic Cells and 5-fluorouracil Elicits Augmented NK Cell-mediated Antitumor Activity Through the Tumor Necrosis Factor-α Pathway

4区 · 医学

Article

作者: Takahara, Akitaka ; Aiba, Keisuke ; Sagawa, Yukiko ; Yagita, Hideo ; Homma, Sadamu ; Nagasaki, Eijiro ; Koido, Shigeo ; Tajiri, Hisao

Antitumor effects and mechanism of combined therapy with a dendritic cell (DC) vaccine and fluorouracil (5-FU) were investigated. Cytotoxic activity against MC38 cells, untreated or pretreated with 5-FU, was examined in splenocytes from mice inoculated with DCs: DCs pulsed with MC38 lysate or treated with LPS or both and untreated DCs. Inoculation with all types of DCs induced the significant cytotoxic activity of splenocytes, and pretreatment of MC38 cells with 5-FU significantly enhanced the cytotoxic activity of splenocytes. Depletion of natural killer (NK) cells, but not of CD8 or CD4 T cells, in the splenocytes from DC (without MC38 lysate-pulse or LPS treatment thereafter)-inoculated mice decreased the cytotoxic activity. The cytotoxic effect was eliminated by treatment with a monoclonal antibody (mAb) against tumor necrosis factor (TNF)-alpha and was partially inhibited by concanamycin A. Inoculation of mice with DCs upregulated TNFalpha expression on NK cells. MC38 cells pretreated with 5-FU exhibited enhanced expression of procaspase 8 and efficiently underwent apoptosis by TNF-alpha with activation of caspase 8. Although treatment with 5-FU upregulated Rae-1 expression on MC38 cells, the NK-cell-mediated cytotoxic activity was not suppressed by treatment with an anti-Rae-1 mAb or an antinatural killer group 2D mAb or both. These results indicate that combined therapy with a DC vaccine and 5-FU is a promising strategy for cancer treatment mediated by the tumoricidal activity of NK cells through the TNF-alpha pathway.

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适应症	最高研发状态	国家/地区	公司	日期
卵巢上皮癌	临床2期	荷兰	Radboud University Medical Center	2023-03-17
转移性子宫内膜恶性肿瘤	药物发现	荷兰	Radboud University Medical Center	2019-04-08

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


SITC2019	N/A	晚期胰腺腺癌 WT1 \| MUC1	23	DC vaccination+OK-432+GEM	積簾積壓範鏇簾蓋膚廠(衊鏇壓窪憲獵膚簾構製) = The treatment was well tolerated and none of the patients experienced more than grade 3 adverse events during the treatment period 願遞網窪鹽廠膚製廠選 (壓醖鑰鹹願襯憲艱壓壓 )	积极	2019-11-01
				DC vaccination+OK-432+S-1