RR001 in combination with chemotherapy for patients with locally advanced pancreatic adenocarcinoma: open-label, non-randomized dose escalation phase I/IIa study - SNIPER

开始日期2023-02-07

申办/合作机构

Rigenerand Srl

100 项与 RR-001 相关的临床结果

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100 项与 RR-001 相关的转化医学

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100 项与 RR-001 相关的专利（医药）

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项与 RR-001 相关的文献（医药）

2023-06-01·Cytotherapy

Impact of soluble tumor necrosis factor-related apoptosis-inducing ligand released by engineered adipose mesenchymal stromal cells on white blood cells.

Article

作者: Grisendi, Giulia ; Casari, Giulia ; Ceccherelli, Giovanni Battista ; Chiavelli, Chiara ; Murgia, Alba ; Baschieri, Maria Cristina ; Neri, Giovanni ; Spano, Maria Carlotta ; Masciale, Valentina ; D'Esposito, Angela ; Dall'Ora, Massimiliano ; Prapa, Malvina ; Dominici, Massimo ; Melandri, Aurora

BACKGROUND AIMSThe proapoptotic protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is physiologically expressed by immune cells and performs regulatory functions in infections, autoimmune diseases and cancer, where it acts as a tumor suppressor. Adipose-derived mesenchymal stromal cells (AD-MSCs) also may play immunomodulatory roles in both primary and acquired immune responses. We have previously demonstrated the efficacy of an anticancer gene therapy based on AD-MSC engineered to secrete a soluble TRAIL variant (sTRAIL) against pancreatic cancer. However, the impact of AD-MSC sTRAIL on leukocyte subsets has been not yet considered also to predict a possible immunotoxicity profile in the clinical translation of this cell-based anticancer strategy.METHODSMonocytes, polymorphonuclear cells and T lymphocytes were freshly isolated from the peripheral blood of healthy donors. Immunophenotype and functional (DR4 and DR5) and decoy (DcR1 and DcR2) TRAIL receptors were tested by flow cytometry. The viability of white blood cells treated with sTRAIL released by gene-modified AD-MSC or co-cultured with AD-MSC sTRAIL was then evaluated by both metabolic assays and flow cytometry. In addition, cytokine profile in co-cultures was analyzed by multiplex enzyme-linked immunosorbent assay.RESULTSMonocytes and polymorphonuclear cells showed high positivity for DR5 and DcR2, respectively, whereas T cells revealed negligible expression of all TRAIL receptors. Irrespective of TRAIL receptors' presence on the cell membrane, white blood cells were refractory to the proapoptotic effect displayed by sTRAIL secreted by gene-modified AD-MSC, and direct cell-to-cell contact with AD-MSC sTRAIL had negligible impact on T-cell and monocyte viability. Cytokine crosstalk involving interleukin 10, tumor necrosis factor alpha, and interferon gamma secreted by T lymphocytes and vascular endothelial growth factor A and interleukin 6 released by AD-MSC was highlighted in T-cell and AD-MSC sTRAIL co-cultures.CONCLUSIONSIn summary, this study demonstrates the immunological safety and thus the clinical feasibility of an anticancer approach based on AD-MSC expressing the proapoptotic molecule sTRAIL.

2016-08-01·Acta Pharmacologica Sinica1区 · 医学

Dendritic cells serve as a “Trojan horse” for oncolytic adenovirus delivery in the treatment of mouse prostate cancer

1区 · 医学

Article

作者: Wang, Zi-Ming ; Li, Zhao-Lun ; Liang, Xuan ; Chong, Tie ; Li, He-Cheng

AIMAdenovirus-mediated gene therapy is a novel therapeutic approach for the treatment of cancer, in which replication of the virus itself is the anticancer method. However, the success of this novel therapy is limited due to inefficient delivery of the virus to the target sites. In this study, we used dendritic cells (DCs) as carriers for conditionally replicating adenoviruses (CRAds) in targeting prostate carcinoma (PCa).METHODSFour types of CRAds, including Ad-PC (without PCa-specific promoter and a recombinant human tumor necrosis factor, rmhTNF, sequence), Ad-PC-rmhTNF (without PCa-specific promoter), Ad-PPC-NCS (without an rmhTNF sequence) and Ad-PPC-rmhTNF, were constructed. The androgen-insensitive mouse PCa RM-1 cells were co-cultured with CRAd-loading DCs, and the viability of RM-1 cells was examined using MTT assay. The in vivo effects of CRAd-loading DCs on PCa were evaluated in RM-1 xenograft mouse model.RESULTSTwo PCa-specific CRAds (Ad-PPC-NCS, Ad-PPC-rmhTNF) exhibited more potent suppression on the viability of RM-1 cells in vitro than the PCa-non-specific CRAds (Ad-PC, Ad-PC-rmhTNF). In PCa-bearing mice, intravenous injection of the PCa-specific CRAd-loading DCs significantly inhibited the growth of xenografted tumors, extended the survival time, and induced T-cell activation. Additionally, the rmhTNF-containing CRAds exhibited greater tumor killing ability than CRAds without rmhTNF.CONCLUSIONDCs may be an effective vector for the delivery of CRAds in the treatment of PCa.

2014-06-01·Artificial Cells, Nanomedicine, and Biotechnology2区 · 工程技术

Experiment research on inhibition of glioma with sTRAIL in vitro

2区 · 工程技术

ArticleOA

作者: Jian Xu ; Zhaojian Li ; Yihe Dou ; Yangang Wang ; Peng Sun ; Qinghai Meng

We report that adenovirus mediated TNF-related apoptosis-inducing ligand (TRAIL) influenced the cell growth and cell cycle in the glioma cells in vitro. After being infected with the Ad-sTRAIL, U251 cell growth was inhibited. The expression of sTRAIL was detected using immunofluorescence. The higher rate of apoptosis was demonstrated using short-term microculture tetrazoliun (MTT) assay and flow cytometry. The rate of Ad-sTRAIL-inducing U251 cell apoptosis was increased depending on the dosage and the time. The apoptosis of G0/G1 and S phase cells was more significant than that of the control groups. The growth and proliferation of U251 cell line was inhibited after the infection of Ad-sTRAIL. It is dose- and time dependent.

100 项与 RR-001 相关的药物交易

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