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pBABEpuro_hnRNPA_alpha Retroviral Vector

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[#RTV-340] pBABEpuro_hnRNPA_alpha Retroviral Vector

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RTV-340 | pBABEpuro_hnRNPA_alpha Retroviral Vector, 100 µL
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(1) HIV vaccine candidate activation of hypoxia and the inflammasome in CD14 monocytes is associated with a decreased risk of SIV acquisition.[TOP]

Pubmed ID :29785023
Publication Date : //
Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)-SIV, DNA-SIV and Ad26-SIV vaccine prime modalities together with two ALVAC-SIV + gp120 protein boosts to reduce the risk of SIV acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14CD16 monocytes, gut-homing CCR5-negative CD4 T helper 2 (T2) cells and antibodies to variable region 2 correlated with a decreased risk of SIV acquisition. By contrast, signal transducer and activator of transcription 3 activation in CD16 monocytes was associated with an increased risk of virus acquisition. The Ad26 prime regimen induced the accumulation of CX3CR1CD163 macrophages in lymph nodes and of long-lasting CD4 T17 cells in the gut and lungs. Our data indicate that the selective engagement of monocyte subsets following a vaccine prime influences long-term immunity, uncovering an unexpected association of CD14 innate monocytes with a reduced risk of SIV acquisition.

Authors : Vaccari Monica, Fourati Slim, Gordon Shari N, Brown Dallas R, Bissa Massimilano, Schifanella Luca, Silva de Castro Isabela, Doster Melvin N, Galli Veronica, Omsland Maria, Fujikawa Dai, Gorini Giacomo, Liyanage Namal P M, Trinh Hung V, McKinnon Katherine M, Foulds Kathryn E, Keele Brandon F, Roederer Mario, Koup Richard A, Shen Xiaoying, Tomaras Georgia D, Wong Marcus P, Munoz Karissa J, Gach Johannes S, Forthal Donald N, Montefiori David C, Venzon David J, Felber Barbara K, Rosati Margherita, Pavlakis George N, Rao Mangala, Sekaly Rafick-Pierre, Franchini Genoveffa,



(2) Replacement of feline foamy virus bet by feline immunodeficiency virus vif yields replicative virus with novel vaccine candidate potential.[TOP]

Pubmed ID :29769087
Publication Date : //
Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Through different mechanisms of action, but with similar consequences, spumaviral feline foamy virus (FFV) Bet and lentiviral feline immunodeficiency virus (FIV) Vif counteract feline APOBEC3 (feA3) restriction factors that lead to hypermutation and degradation of retroviral DNA genomes. Here we examine the capacity of vif to substitute for bet function in a chimeric FFV to assess the transferability of anti-feA3 factors to allow viral replication.

Authors : Ledesma-Feliciano Carmen, Hagen Sarah, Troyer Ryan, Zheng Xin, Musselman Esther, Slavkovic Lukic Dragana, Franke Ann-Mareen, Maeda Daniel, Zielonka Jörg, Münk Carsten, Wei Guochao, VandeWoude Sue, Löchelt Martin,



(3) Durable Complete Responses in Some Recurrent High Grade Glioma Patients Treated with Toca 511 & Toca FC.[TOP]

Pubmed ID :29762717
Publication Date : //
Vocimagene amiretrorepvec (Toca 511) is an investigational gamma-retroviral replicating vector encoding cytosine deaminase that, when used in combination with extended-release 5-fluorocytosine (Toca FC), results preclinically in local production of 5-fluorouracil, depletion of immune-suppressive myeloid cells, and subsequent induction of anti-tumor immunity. Recurrent high grade glioma (rHGG) patients have a high unmet need for effective therapies that produce durable responses lasting more than 6 months. In this setting, relapse is nearly universal and most responses are transient.

Authors : Cloughesy Timothy F, Landolfi Joseph, Vogelbaum Michael A, Ostertag Derek, Elder James B, Bloomfield Stephen, Carter Bob, Chen Clark C, Kalkanis Steven N, Kesari Santosh, Lai Albert, Lee Ian Y, Liau Linda M, Mikkelsen Tom, Nghiemphu Phioanh, Piccioni David, Accomando William, Diago Oscar R, Hogan Daniel J, Gammon Dawn, Kasahara Noriyuki, Kheoh Thian, Jolly Douglas J, Gruber Harry E, Das Asha, Walbert Tobias,



(4) Therapeutic activity of retroviral replicating vector-mediated prodrug activator gene therapy for pancreatic cancer.[TOP]

Pubmed ID :29735994
Publication Date : //
Toca 511, a retroviral replicating vector (RRV) encoding the yeast cytosine deaminase (yCD) prodrug activator gene, which mediates conversion of the prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU), is currently being evaluated in Phase II/III clinical trials for glioma, and showing highly promising evidence of therapeutic activity. Here we evaluated RRV-mediated prodrug activator gene therapy as a new therapeutic approach for pancreatic ductal adenocarcinoma (PDAC). RRV spread rapidly and conferred significant cytotoxicity with prodrug in a panel of PDAC cells. Efficient intratumoral replication and complete inhibition of tumor growth upon 5-FC administration were observed in both immunodeficient and immunocompetent subcutaneous PDAC models. Biodistribution of RRV was highly restricted in normal tissues, especially in immunocompetent hosts. Tumor growth inhibition by Toca 511 followed by 5-FC was also confirmed in the orthotopic PDAC model. This study provides the first proof-of-concept for application of Toca 511 and Toca FC (extended release 5-FC) to the treatment of human PDAC, and provided support for inclusion of PDAC in a Phase I study evaluating Toca 511 in various systemic malignancies, (NCT02576665), which has recently been initiated.

Authors : Inoko Kazuho, Hiraoka Kei, Inagaki Akihito, Takahashi Mizuna, Kushibiki Toshihiro, Hontani Koji, Takano Hironobu, Sato Shoki, Takeuchi Shintaro, Nakamura Toru, Tsuchikawa Takahiro, Shichinohe Toshiaki, Gruber Harry E, Jolly Douglas J, Kasahara Noriyuki, Hirano Satoshi,



(5) A CRISPR knockout screen identifies SETDB1-target retroelement silencing factors in embryonic stem cells.[TOP]

Pubmed ID :29728365
Publication Date : //
In mouse embryonic stem cells (mESCs), the expression of provirus and endogenous retroelements is epigenetically repressed. Although many cellular factors involved in retroelement silencing have been identified, the complete molecular mechanism remains elusive. In this study, we performed a genome-wide CRISPR screen to advance our understanding of retroelement silencing in mESCs. The Moloney murine leukemia virus (MLV)-based retroviral vector MSCV-, which is repressed by the SETDB1TRIM28 pathway in mESCs, was used as a reporter provirus, and we identified more than 80 genes involved in this process. In particular, ATF7IP and the BAF complex components are linked with the repression of most of the SETDB1 targets. We characterized two factors, MORC2A and RESF1, of which RESF1 is novel molecule in retroelement silencing. Although both factors are recruited to repress provirus, their roles in repression are different. MORC2A appears to function dependent on repressive epigenetic modifications, while RESF1 regulates repressive epigenetic modifications associated with SETDB1. Our genome-wide CRISPR screen cataloged genes which function at different levels in silencing of SETDB1-target retroelements and provides a useful resource for further molecular studies.

Authors : Fukuda Kei, Okuda Akihiko, Yusa Kosuke, Shinkai Yoichi,



(6) Effect of Tissue Factor on Colorectal Cancer Stem Cells.[TOP]

Pubmed ID :29715083
Publication Date : //
Tissue factor (TF) expression increases cancer stem cell (CSC) activity in breast and lung cancer. There are ongoing studies focused on targeting CSCs via anti-TF treatment, for breast and lung cancer therapy. Herein, the aim was to determine whether targeting TF could have an anti-CSC therapeutic role in colorectal cancer (CRC).

Authors : Clouston Hamish William, Rees Peter Adam, Lamb Rebecca, Duff Sarah Elizabeth, Kirwan Cliona Clare,



(7) Gene Therapy as a Curative Option for β-Thalassemia.[TOP]

Pubmed ID :29669229
Publication Date : //

Authors : Biffi Alessandra,



(8) Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia.[TOP]

Pubmed ID :29669226
Publication Date : //
Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (β) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia.

Authors : Thompson Alexis A, Walters Mark C, Kwiatkowski Janet, Rasko John E J, Ribeil Jean-Antoine, Hongeng Suradej, Magrin Elisa, Schiller Gary J, Payen Emmanuel, Semeraro Michaela, Moshous Despina, Lefrere Francois, Puy Hervé, Bourget Philippe, Magnani Alessandra, Caccavelli Laure, Diana Jean-Sébastien, Suarez Felipe, Monpoux Fabrice, Brousse Valentine, Poirot Catherine, Brouzes Chantal, Meritet Jean-François, Pondarré Corinne, Beuzard Yves, Chrétien Stany, Lefebvre Thibaud, Teachey David T, Anurathapan Usanarat, Ho P Joy, von Kalle Christof, Kletzel Morris, Vichinsky Elliott, Soni Sandeep, Veres Gabor, Negre Olivier, Ross Robert W, Davidson David, Petrusich Alexandria, Sandler Laura, Asmal Mohammed, Hermine Olivier, De Montalembert Mariane, Hacein-Bey-Abina Salima, Blanche Stéphane, Leboulch Philippe, Cavazzana Marina,



(9) [Relationship between DNMT1 and Methylation of SHP-1 Promoter 2 in K562 Cells].[TOP]

Pubmed ID :29665905
Publication Date : //
To investigate the relationship of DNA methyltransferase 1 ( DNMT1 ) with hematopoietic cell phosphatase (SHP-1) gene expression and promoter 2 methylation status in cell line K562.

Authors : Liu Xue-Dong, Liu Xiao, Guo Xiu-Fen, Luo Jian-Min, Li Ying-Hua,



(10) The Hard Way towards an Antibody-Based HIV-1 Env Vaccine: Lessons from Other Viruses.[TOP]

Pubmed ID :29662026
Publication Date : //
Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of "classical" vaccine approaches, which are mostly due to the biological properties of the virus itself. HIV-1 has developed multiple mechanisms of immune escape, which also account for vaccine failure. So far, no vaccine candidate has been able to induce broadly neutralizing antibodies (bnAbs) against primary patient viruses from different clades. However, such antibodies were identified in a subset of patients during chronic infection and were shown to protect from infection in animal models and to reduce viremia in first clinical trials. Their detailed characterization has guided structure-based reverse vaccinology approaches to design better HIV-1 envelope (Env) immunogens. Furthermore, conserved Env epitopes have been identified, which are promising candidates in view of clinical applications. Together with new vector-based technologies, considerable progress has been achieved in recent years towards the development of an effective antibody-based HIV-1 vaccine.

Authors : Ringel Oliver, Vieillard Vincent, Debré Patrice, Eichler Jutta, Büning Hildegard, Dietrich Ursula,