CSF-2R stimulants(Granulocyte-macrophage colony-stimulating factor receptor stimulants), PDL1 inhibitors(Programmed death-ligand 1 inhibitors), Cell death stimulants

+ [1]

Therapeutic Areas

Neoplasms

Active Indication

Solid tumor

Inactive Indication-

Originator Organization

Wuhan Binhui Biopharmaceutical Co., Ltd.

Active Organization

Wuhan Binhui Biopharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhaseIND Application

First Approval Date-

Regulation-

100 Clinical Results associated with BS008

100 Translational Medicine associated with BS008

100 Patents (Medical) associated with BS008

Literatures (Medical) associated with BS008

25 Feb 2024·Sheng wu gong cheng xue bao = Chinese journal of biotechnology

[Replication and expression of oncolytic herpes simplex virus type Ⅱ in tumors].

Article

Author: Cai, Qiying ; Zhang, Siqi ; Liu, Huajuan ; Liu, Binlei

This study aimed to measure the duration and replication level of oncolytic herpes simplex virus type 2 (oHSV2) at the tumor injection site in BALB/c mice. Additionally, the expression level of human granulocyte macrophage colony-stimulating factor (hGM-CSF) and HSV-2 antibody in the serum was also measured. High and low doses of oHSV2-Fluc (firefly luciferin, Fluc) were injected into the mice's tumors to track the change and duration of fluorescence expression. The copy number of oHSV2 gene in tumor tissues was determined using quantitative real-time polymerase chain reaction (qPCR). Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of hGM-CSF and HSV-2 antibody in the serum. The tumor volume in the high-dose group was significantly lower than that in the control group (P < 0.01). Intratumor injection of oHSV2-Fluc showed that the carried Fluc could continue to express in the tumor, with fluorescence still detectable at day 11 and declining to undetectable level by day 18. The mRNA expression of oHSV2 was detected in tumor tissues of both high and low dose groups on day 9 using qPCR. ELISA results showed that the levels of HSV2 antibody and hGM-CSF in both high and low dose groups were significantly increased compared to the control group (P < 0.05) after collecting orbital blood. These findings suggest that oHSV2 can replicate in the tumor and sustainably express exogenous factors, thus effectively targeting and killing the tumor. Furthermore, intratumoral injection of oHSV2 resulted in higher levels of hGM-CSF and HSV-2 antibodies found in the mice's serum.

31 Dec 2023·Autoimmunity

Oncolytic virus oHSV2 combined with PD-1/PD-L1 inhibitors exert antitumor activity by mediating CD4 + T and CD8 + T cell infiltration in the lymphoma tumor microenvironment

Article

Author: Guo, Yiwei ; Zhao, Lina ; Zhang, Jingbo ; Fang, Huiying ; Guo, Xiuchen

A novel therapeutic regimen showed that the oncolytic type II herpes simplex virus (oHSV2) was able to prevent colorectal cancer growth, recurrence, and metastasis. However, no study has yet explored whether oHSV2 has an impact on the development of diffuse large B-cell lymphoma (DLBCL). We chose the clinical chemotherapeutic drug doxorubicin (DOX) as a positive control to evaluate the effect of oHSV2 infection on the apoptotic, invasive, and proliferative capacity of DLBCL cells. We next further explored the therapeutic efficacy of oncolytic virus oHSV2 or DOX in DLBCL tumor bearing BALB/c mice, and evaluated the infiltration of CD8 + T cells and CD4 + T cells in tumor tissues. A pathological approach was used to explore the effects of oHSV2 on various organs of tumor bearing mice, including the heart, liver, and kidney. Next, SU-DHL-4 cells were co-cultured with cytotoxic T lymphocytes (CTLs) to mimic the tumor immune microenvironment (TME), to explore the impact of oHSV2 on the immune environment at the cellular level, and then analyzed the relationship between oHSV2 and the PD-1/PD-L1 immune-checkpoint. Subsequently, we further validated the efficacy of combined oHSV2 and PD-L1 treatment on transplanted tumor growth in mice at the in vivo level. DLBCL cells were sensitive to the action of the oncolytic virus oHSV2, and the decline in their proliferative activity showed a time-and dose-dependent manner. oHSV2 and DOX intervention preeminently increased the cell apoptosis, restrained cell proliferation and invasion, with the greatest changes occurring in response to oHSV2 infection. oHSV2 application effectively improved the immune status of the tumor microenvironment, favoring the invasion of CD8 + T and CD4 + T cells, thereby enhancing their antitumor effects. Besides, oHSV2 treatment has a safety profile in the organs of tumor bearing mice and indeed inhibits the PD-1/PD-L1 immune checkpoint in DLBCL. Interestingly, the combination of oHSV2 and PD-L1 antibodies results in more profound killing of DLBCL cells than oHSV2 infection alone, with a significant increase in the proportion of CD4 + T cells and CD8 + T cells. The antitumor effect was the best after combining oHSV2 and PD-L1 antibodies, suggesting that the combination therapy of oHSV2 and PD-L1 would have a better prospect for clinical application.

01 Dec 2022·Virology JournalQ3 · MEDICINE

A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy

Q3 · MEDICINE

ArticleOA

Author: Wang, Yang ; Liu, Binlei ; Dong, Shuang ; Fang, Zhizheng ; Duan, Haixiao ; Yang, Junhan ; Zhang, Siqi ; Li, Yuying ; Liu, Biao ; Cai, Linkang ; Hu, Han

AbstractBackgroundSelectively replicating herpes simplex virus-2 (HSV-2) vector is a promising treatment for cancer therapy. The insertion of multiple transgenes into the viral genome has been performed to improve its oncolytic activity.MethodsHerein, we simultaneously constructed five “armed” oncolytic viruses (OVs), designated oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19. These OVs delete theICP34.5andICP47genes with the insertion of transgenes into the deletedICP34.5locus. The anti-tumor efficacy in vivo was tested in the syngeneic 4T1 and CT26 tumor-bearing mice model.ResultsThe OVs showed comparable oncolytic capability in vitro. The combination therapy of oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19 exhibited the highest tumor inhibition efficacy compared with the treatment of single OV or two OVs combination.ConclusionsThe OVs armed with different transgenes combination therapy also named 5-valent oHSV2 (also called cocktail therapy) might be an effective therapeutic strategy for solid tumors.

100 Deals associated with BS008

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	IND Application	CN	Wuhan Binhui Biopharmaceutical Co., Ltd.	-

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