Delving into the Latest Updates on Recombinant oncolytic herpes simplex virus type 1(Shanghai Yunying Medical Technology) with Synapse

Overview

Basic Info

Drug Type

Oncolytic virus

Synonyms

Target

Mechanism

CD3 inhibitors(T cell surface glycoprotein CD3 inhibitors), CD86 inhibitors(Cluster of differentiation 86 inhibitors), PD-1 inhibitors(Programmed cell death protein 1 inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [7]

Active Indication

Brain CancerKidney NeoplasmsMelanoma+ [25]

Inactive Indication-

Originator Organization

Shanghai Yunying Medical Technology Co., Ltd.Startup

Active Organization

Shanghai Yunying Medical Technology Co., Ltd.StartupShanghai Yunying Biomedical Technology Co., Ltd.

Inactive Organization-

Drug Highest PhaseEarly Phase 1

First Approval Date-

Regulation-

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After a long period of endeavor, immunotherapy has become the mainstream of cancer therapies. This success is mostly ascribed to immune checkpoint blockade, chimeric antigen receptor-transduced T cell therapies, and bispecific antibodies. However, these methods have been effective or applicable to only a limited proportion of patients so far. Thus, further development of broadly applicable and effective immunotherapies is eagerly anticipated. Given that innate immunity is key to the induction of robust adaptive immunity and that the immunosuppressive tumor microenvironment is a major hurdle to overcome, intratumoral immunotherapy in which delivery of immunostimulatory microbial agents to the tumor site triggers innate immunity in situ is a rational strategy. There has been a plethora of preclinical and clinical trials conducted involving the delivery of either mimetics of viral nucleic acids or oncolytic viruses intratumorally to trigger innate immunity via various nucleic acid sensors in the tumor site. Many of these have shown significant antitumor effects in mice, particularly in combination with immune checkpoint blockade. Oncolytic herpes simplex virus type 1 has been approved for the treatment of advanced melanoma in the United States and Europe and of glioblastoma in Japan. Whereas direct intratumoral administration has mainly been chosen as a delivery route, several promising compounds amenable to systemic administration have been developed. Intratumoral delivery of immunostimulatory agents will become an important option for cancer immunotherapy as an off-the-shelf, broadly applicable, and rational strategy that exploits the physiology of immunity, namely anti-microbial immunity.

01 Dec 2020·Cancer LettersQ1 · MEDICINE

Antitumor efficacy of oncolytic HSV-1 expressing cytosine deaminase is synergistically enhanced by DPD down-regulation and EMT inhibition in uveal melanoma xenograft

Q1 · MEDICINE

Article

Author: Zhu, Guidong ; Zhang, Junwen ; Zhao, Mingwei ; Liu, Sisi ; Zhang, Qing ; Su, Xiaodong ; Liu, Fusheng ; Zhu, Li ; Fang, Sheng

Uveal melanoma (UM) is the most common intraocular tumor in adults and has a high incidence of metastases. Possible treatments remain limited in UM with enucleation and radiation, leading to poor prognosis in this chemo-resistant carcinoma. Thus, urging demand for novel treatment is needed. We examined the antitumor efficacy of a new recombinant oncolytic herpes simplex virus type 1 (oHSV-1) armed with E.coli cytosine deaminase (CD). We determined the efficacy of the oncolytic virus in UM cell lines. In vivo experiments showed that oHSV-CD/5-fluorocytosine (5-FC) treatment reduce tumor volume and prolonged survival. We further demonstrated the molecular mechanisms of oHSV-CD/5-FC treatment. The oncolytic virus down-regulated IL-6 expression and thereby reversed the epithelial-mesenchymal transition (EMT) phenotype. Dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-fluorouracil (5-FU) metabolism, was also down-regulated. Therefore, the efficacy of oHSV-CD/5-FC was synergistically enhanced by DPD down-regulation and EMT inhibition. This study provides solid evidence for the antitumor efficacy of oHSV-CD/5-FC treatment in vitro and in vivo. The molecular mechanisms of this treatment may bring a new therapeutic approach for future treatment of UM.

01 Jan 2019·Clinical Cancer ResearchQ1 · MEDICINE

Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy

Q1 · MEDICINE

Article

Author: Speranza, Maria C. ; Freeman, Gordon J. ; Ito, Hirotaka ; Lawler, Sean E. ; Fernandez, Soledad ; Passaro, Carmela ; Nakashima, Hiroshi ; Bhaskaran, Vivek ; McNulty, John ; Shah, Khalid ; Alayo, Quazim ; Chiocca, E. Antonio ; Grauwet, Korneel ; DeLaura, Isabel ; Mineo, Marco ; McLaughlin, Eric ; Reardon, David A. ; Goins, William

AbstractPurpose:Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM.Experimental Design:NG34scFvPD-1 expresses the human GADD34 gene transcriptionally controlled by the Nestin promoter to allow replication in GBM cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In vitro cytotoxicity and replication assays were performed to measure NG34scFvPD-1 oncolysis, and scFvPD-1 expression and secretion were determined. In vivo survival studies using orthotopic mouse GBM models were performed to evaluate the therapeutic potency of NG34scFvPD-1.Results:NG34scFvPD-1–infected GBM cells express and secrete scFvPD-1 that binds mouse PD-1. The introduction of the scFvPD-1 sequence in the viral backbone does not alter the oncolytic properties of NG34scFvPD-1. In situ NG34scFvPD-1 treatment improved the survival with a tail of durable survivorship in 2 syngeneic immunocompetent mouse models of GBM. Mice that survived the first GBM challenge rejected the second challenge of GBM when implanted in the contralateral hemisphere. However, this was not true when athymic mice were employed as the recipients of the second challenge, consistent with the need for an intact immune system to obtain a memory response.Conclusions:NG34scFvPD-1 treatment induces a durable antitumor response in 2 preclinical mouse models of GBM with evidence for antitumor memory.

100 Deals associated with Recombinant oncolytic herpes simplex virus type 1(Shanghai Yunying Medical Technology)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	02 Mar 2023
Carcinoma	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	02 Mar 2023
Liver Cancer	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	02 Mar 2023
Pancreatic Cancer	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	02 Mar 2023
Advanced cancer	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	06 Feb 2023
Endometrial Carcinoma	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	06 Feb 2023
Uterine Cervical Cancer	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	06 Feb 2023
Fallopian Tube Carcinoma	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	02 Dec 2022
Peritoneal Neoplasms	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	02 Dec 2022
Recurrent ovarian cancer	Phase 1	CN	Shanghai Yunying Medical Technology Co., Ltd.Startup	02 Dec 2022