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Last update 23 Jan 2025

Viral fusion proteins x CD4

Last update 23 Jan 2025

Basic Info

Related Targets

Viral fusion proteinsCD4

Drugs associated with Viral fusion proteins x CD4

Ibalizumab-UIYK

Target

CD4 x Viral fusion proteins

Mechanism

CD4 inhibitors [+1]

Active Org.

Theratechnologies, Inc. [+1]

Originator Org.

Biogen, Inc.

Active Indication

HIV Infections

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date06 Mar 2018

Clinical Trials associated with Viral fusion proteins x CD4

NCT05890963

/ RecruitingPhase 1IIT

Phase 1b Single Dose Clinical Trial of a Novel Long-Acting Bispecific Antibody in People With HIV to Inform Development for HIV Pre- and Post-Exposure Prophylaxis

This is an open-label phase 1b clinical trial enrolling people living with HIV (PLWH) who are antiretroviral therapy (ART)-naïve or have not been on ART for > 24 weeks. This study will enroll PLWH to assess the safety, tolerability, and antiviral effect of bispecific and long-acting bNAbs, alone and in combination. The study will be conducted as a single center study at National Institute for Medical Research-Mbeya Medical Research Center (NIMR-MMRC) in Mbeya, Tanzania.
20 PLWH will be sequentially enrolled into one of 5 arms, each arm comprised of 4 participants. Sequential enrollment will occur in the following order:
* Arm 1 will receive standard daily oral ART.
* Arm 2 will receive a single dose of 10E8.4/iMab 600mg intravenous injection (IV).
* Arm 3 will receive a single dose of 10E8.4/iMab 600mg intramuscular injection (IM).
* Arm 4 will receive a single dose of 10E8.4/iMab 1800mg IV.
* Arm 5 will receive a single dose of combination therapy with both 10E8.4/iMab 1800mg IV and VRC07-523LS 1200mg IV.

Start Date28 Nov 2023

Sponsor / Collaborator

Columbia University

[+1]

NCT05495204

/ CompletedNot Applicable

External Comparison of Effectiveness of Ibalizumab in Clinical Trials vs. Other HTE Regimens in OPERA

Among heavily treatment experienced people living with HIV, the virologic effectiveness of ibalizumab + optimized background regimen from two clinical trials will be compared to non-ibalizumab-containing regimens in routine clinical care in the OPERA cohort.

Start Date05 Aug 2022

Sponsor / Collaborator

Epividian, Inc.

[+1]

100 Clinical Results associated with Viral fusion proteins x CD4

100 Translational Medicine associated with Viral fusion proteins x CD4

0 Patents (Medical) associated with Viral fusion proteins x CD4

Literatures (Medical) associated with Viral fusion proteins x CD4

01 Jan 2023·Burns & trauma

p53 promotes the expansion of regulatory T cells via DNMT3a- and TET2- mediated Foxp3 expression in sepsis.

Article

Author: Zhang, Hui ; Dong, Ning ; Yao, Yongming ; Wu, Tiantian ; Wu, Yao ; Ren, Chao

BackgroundImmunosuppression is an important characteristic of sepsis and is closely related to poor outcomes. Regulatory T cells (Tregs) contribute to immune suppression by inhibiting effector T cell (Teff) proliferation and differentiation. We aimed to investigate the role of p53 in Treg expansion after sepsis.MethodsWe constructed a sepsis model in wild-type (WT) and p53^f/f/CD4-Cre⁺ mice by cecal ligation and puncture (CLP) and evaluated the proportions of CD4⁺CD25⁺ Foxp3⁺ Tregs by flow cytometry. The expression levels of forkhead/winged helix transcription factor p3 (Foxp3), DNA methyltransferase enzyme (DMNT)3a and ten-eleven translocation (TET)2 were examined using quantitative real-time PCR and Western blot analysis. Treg-specific demethylation region (TSDR) methylation sites in cells were analyzed by bisulfite-sequencing PCR. Furthermore, the direct binding of p53 to the Dnmt3a and TET2 promoters was illustrated using a luciferase assay. The suppressive ability of Tregs was indicated by enzyme-linked immunosorbent assay analysis of cytokine levels and the proliferation of cocultured Teffs. Finally, mortality rates after CLP were compared among WT and p53^f/f/CD4-Cre⁺ mice.ResultsThe proportion of CD4⁺CD25⁺ Foxp3⁺ Tregs was significantly reduced in p53^f/f/CD4-Cre⁺ mice compared to WT mice after CLP. The enhanced expression of Foxp3 in WT mice was downregulated in the p53^f/f/CD4-Cre⁺ group. We found decreased DMNT3a and increased TET2 levels after CLP. However, the dysregulation of DNMT3a and TET2 was significantly reversed in p53^f/f/CD4-Cre⁺ mice. TSDR underwent increased demethylation in p53^f/f/CD4-Cre⁺ mice. Luciferase activity indicated direct binding of p53 to the promoter regions of DNMT3a and TET2 to regulate their transcription. Consequently, Tregs from p53^f/f/CD4-Cre⁺ CLP mice exhibited limited suppressive ability, as indicated by the reduced production of transforming growth factor-β and interleukin 10 (IL-10). In the coculture system, Teffs showed preserved production of IL-2, differentiation into Th1 cells and proliferation in the presence of Tregs isolated from p53^f/f/CD4-Cre⁺ CLP mice. Finally, the mortality rate of the p53^f/f/CD4-Cre⁺ group after CLP was significantly reduced in comparison to that of the WT group.Conclusionp53 appears to be critical for Foxp3 expression and consequent Treg expansion by regulating the induction of DNMT3a and TET2, thereby resulting in Foxp3-TSDR demethylation in the context of sepsis.

01 Jul 2021·Cell ProliferationQ2 · BIOLOGY

A novel mouse model for liver metastasis of prostate cancer reveals dynamic tumour‐immune cell communication

Q2 · BIOLOGY

ArticleOA

Author: Wang, Deng ; Wang, Jinming ; Xin, Zhixiang ; Cheng, Chaping ; Chen, Xinyu ; Zhang, Kai ; Xu, Penghui ; He, Yuman ; Zhu, Helen He ; Gao, Wei‐Qiang ; Ji, ZhongZhong ; Zhao, Huifang ; Liu, Kaiyuan ; Zhang, Pengcheng ; Jing, Na

AbstractObjectivesIn contrast to extensive studies on bone metastasis in advanced prostate cancer (PCa), liver metastasis has been under‐researched so far. In order to decipher molecular and cellular mechanisms underpinning liver metastasis of advanced PCa, we develop a rapid and immune sufficient mouse model for liver metastasis of PCa via orthotopic injection of organoids from PbCre+; rb1f/f;p53f/f mice.Materials and MethodsPbCre+;rb1f/f;p53f/f and PbCre+;ptenf/f;p53f/f mice were used to generate PCa organoid cultures in vitro. Immune sufficient liver metastasis models were established via orthotopic transplantation of organoids into the prostate of C57BL/6 mice. Immunofluorescent and immunohistochemical staining were performed to characterize the lineage profile in primary tumour and organoid‐derived tumour (ODT). The growth of niche‐labelling reporter infected ODT can be visualized by bioluminescent imaging system. Immune cells that communicated with tumour cells in the liver metastatic niche were determined by flow cytometry.ResultsA PCa liver metastasis model with full penetrance is established in immune‐intact mouse. This model reconstitutes the histological and lineage features of original tumours and reveals dynamic tumour‐immune cell communication in liver metastatic foci. Our results suggest that a lack of CD8+ T cell and an enrichment of CD163+ M2‐like macrophage as well as PD1+CD4+ T cell contribute to an immuno‐suppressive microenvironment of PCa liver metastasis.ConclusionsOur model can be served as a reliable tool for analysis of the molecular pathogenesis and tumour‐immune cell crosstalk in liver metastasis of PCa, and might be used as a valuable in vivo model for therapy development.

01 Jun 2020·Cancer Gene TherapyQ2 · MEDICINE

Cancer immunotherapy using the Fusion gene of Sendai virus

Q2 · MEDICINE

Article

Author: Chang, Chin Yang ; Nishikawa, Tomoyuki ; Kaneda, Yasufumi ; Tai, Jiayu A

Inactivated Sendai virus particle (or hemagglutinating virus of Japan envelope; HVJ-E) has been previously reported to possess antitumour properties that activate antitumour immunity. Two glycoproteins, fusion (F) and hemagglutinin-neuraminidase (HN), are present on the surface of HVJ-E. HN is necessary for binding to receptors such as acidic gangliosides, and F induces membrane fusion by associating with membrane lipids. We previously reported that liposomes reconstituted with F but not HN showed antitumour activity by inducing IL-6 secretion in dendritic cells (DCs), suggesting that F protein is capable of eliciting antitumour activity. Here, we attempted to deliver F gene into tumour tissue in mice by electroporation and demonstrated that F gene therapy retarded tumour growth, increased CD4⁺ and CD8⁺ T-cell infiltration into tumours and induced tumour-specific IFN-γ T-cell response. However, neutralisation of IL-6R signalling did not impact F plasmid-mediated antitumour effect. Instead, we found that F plasmid treatment resulted in a significant increase in the secretion of the chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) by tumour-infiltrating T cells. Neutralising antibody against RANTES abolished the antitumour effect of F plasmid treatment in a dose-dependent manner. Thus, F gene therapy may show promise as a novel therapeutic for single or combined cancer immunotherapy.

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