9 participants are expected to be enrolled for this open，Single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with advanced bone and soft tissue tumors.

Start Date12 Jul 2023

Sponsor / Collaborator

Shanghai Yunying Medical Technology Co., Ltd.Startup

[+1]

NCT05961111 / RecruitingEarly Phase 1

An Open, Single-armed, Clinical Safety and Efficacy Study on Oncolytic Virus Injection (R130 OV) for the Treatment of Advanced Solid Tumors

20 participants are expected to be enrolled for this open，Single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with advanced solid tumors.

Start Date24 Jun 2023

Sponsor / Collaborator

Shanghai Yunying Medical Technology Co., Ltd.Startup

NCT05851456 / RecruitingEarly Phase 1

A Clinical Safety and Efficacy Study on Oncolytic Virus Injection (R130) for the Treatment of Relapsed/Refractory Bone and Soft Tissue Tumors

Start Date10 Apr 2023

Sponsor / Collaborator

Shanghai Yunying Medical Technology Co., Ltd.Startup

100 Clinical Results associated with PD-1 x CD86 x CD3

100 Translational Medicine associated with PD-1 x CD86 x CD3

0 Patents (Medical) associated with PD-1 x CD86 x CD3

Literatures (Medical) associated with PD-1 x CD86 x CD3

01 Feb 2023·Toxicology in Vitro

Aryl hydrocarbon receptor knockout and antibody blockade of programmed cell death ligand1 increase co-stimulatory molecules on THP-1 and specific cytokine response of human T cells

Article

Author: Kreutz, Reinhold ; Stahlmann, Ralf ; Sonnenburg, Anna ; Peiser, Matthias

Skin sensitisation involves activation of dendritic cells which activate T cells and induce their clonal expansion. While the first step is covered by OECD-validated new approach methodologies, the latter is not until now. This may be due to a weak dendritic cell activation in vitro that is not strong enough to mediate activation of T cells. Here, we suppressed two inhibitory pathways to overcome this problem. We blocked the Programmed Cell Death (PD) pathway with anti-PD-L1 antibody and knocked out aryl hydrocarbon receptor (AhR) in THP-1 cells by CRISPR/Cas9 technology. Thereby, we reduced AhR⁺ cells to 33% and PD-L1⁺ THP-1 to 5% of the population. In presence of keratinocytes, CD86 and CD54 were elevated on AhR-knockout cells. In coculture with Jurkat T cells, AhR knockout inhibited MIP-1β but induced TNF-α on protein level. In combination with PD-L1 blockade, AhR knockout induced IL-8. In contrast to induction of T cell differentiation evidenced by cytokine release, CD3 and Ki-67 staining revealed no induction of T cell proliferation. In conclusion, a proof-of-principle has been delivered for the usefulness of AhR knockout and PD-L1 blockade in dendritic cells to enlarge the response range of cells in a sensitisation assay for regulatory use.

01 Jan 2023·Journal of inflammation research

NUP62CL as an Immunological and Prognostic Biomarker of Oral Squamous Cell Carcinoma.

Article

Author: Yang, Lei ; Xu, Lijun ; Zhou, Yan ; Zhou, Yongqiang ; Zhou, Xiaorong ; Yu, Xin

BackgroundOral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a high mortality rate and poor prognosis. The exploration and understanding of biomarkers will help to further improve the diagnosis and treatment of OSCC.MethodsTumor tissue samples from 319 OSCC patients were retrospectively collected, along with their clinical information. In combination with bioinformatics tools and multiplex immunohistochemistry (mIHC) analyses, we evaluated NUP62CL protein expression and its relationship to tumor-infiltrating immune cells (TIICs) and immune checkpoints in the tumor microenvironment (TME), as well as its association with clinical features and prognosis of OSCC.ResultsWe identified high-NUP62CL expression in OSCC tissues, and high-NUP62CL protein expression was associated with large tumor size, advanced clinical stage and poor prognosis. In addition, NUP62CL protein expression was positively associated with the abundance of CD3+CD4+ T cells (P<0.01), CD3+CD8+ T cells (P<0.01), CD56+ NK cells (P<0.05), CD68+CD86+ macrophages (P<0.01) and CD68+CD163+ macrophages (P<0.01), as well as the immune checkpoints, including PD-1 (P<0.001), PD-L1 (P<0.001), and CTLA-4 (P<0.001) protein expression.ConclusionIn conclusion, NUP62CL could be an effective prognostic and immunological biomarker for OSCC patients.

01 Jul 2022·Indian Journal of Pharmacology

Immunological factors associated with discordant virological response postcombination antiretroviral therapy in pediatric human immunodeficiency virus infection

Article

Author: Lodha, Rakesh ; Das, Bimal Kumar ; Singh, Ravinder ; Maurya, Shesh Prakash ; Kabra, Sushil Kumar ; Das, Namrata

OBJECTIVES:Evaluation of immunological factors responsible for discordant virological responses postcombination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-positive children aged <5 years.MATERIALS AND METHODS:Immunological profiling of enrolled 30 HIV-positive children was done at enrollment, 6 and 12 months. Flow cytometric analysis was performed for enumeration of counts and percentage of CD4+, CD8+, and CD19+ cells; expression of CD19, CD86, PD-1, CD3, CD8 and CD28 on lymphocytes was evaluated using whole blood staining technique with monoclonal antibodies. HIV-1 viral load was quantified using a real-time polymerase chain reaction. Serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin (IgM), and interleukin (IL)-7 were quantitated using quantitative enzyme-linked immunosorbent assay kits. The HIV-infected children were categorized into virological responders (VRs; HIV-1 plasma viral load <47 copies/mL) and virological nonresponders (VNRs; HIV-1 plasma viral load >1000 copies/mL) following 1-year cART.RESULTS:The frequency of CD28+ CTLs cells was higher (P < 0.0001), and the frequency of CD28-CTLs cells was lower (P < 0.0001) in VRs than VNRs. CD28+ and CD28-CTLs cells correlated with HIV-1 plasma viremia (r = −0.4695, P = 0.01; r = 0.40, P = 0.03, respectively). VRs had higher CD19 percentage (P = 0.04) and count (P = 0.01) than VNRs. CD19+ B cells in the VRs had lower expression of CD86 (P = 0.03) and PD-1 (P = 0.002) than VNRs. VR had lower levels of serum IgG (P = 0.03), IgM (P = 0.04), and IL-7 (P = 0.01) than VNRs.CONCLUSIONS:High baseline B-cell counts, lower serum IgG, IgM, IL-7 levels, lower activation and exhaustion of B cells, and higher frequency of CD28+ CTLs are associated with positive virological response, whereas elevated CD28-CTLs are associated with the poor virological outcomes in HIV-infected children.

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