A clinical study of a replication-competent, recombinant herpes simplex virus type 1 (G47delta) in patients with progressive malignant pleural mesothelioma - A clinical study of G47delta oncolytic virus therapy for progressive malignant pleural mesothelioma

Start Date01 Sep 2018

Sponsor / Collaborator-

JPRN-UMIN000011636 / RecruitingIIT

A clinical study of a replication-competent, recombinant herpes simplex virus type 1 (G47delta) in patients with progressive olfactory neuroblastoma - A clinical study of G47delta oncolytic virus therapy for progressive olfactory neuroblastoma

Start Date06 Sep 2013

Sponsor / Collaborator-

100 Clinical Results associated with Teserpaturev

100 Translational Medicine associated with Teserpaturev

100 Patents (Medical) associated with Teserpaturev

143

Literatures (Medical) associated with Teserpaturev

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

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 Sep 2023·Cancer letters

Photodynamic augmentation of oncolytic virus therapy for central nervous system malignancies

Article

Author: Hasan, Tayyaba ; Uthamacumaran, Abicumaran ; Gokyer, Dilan ; Wakimoto, Hiroaki ; Jabbar, Muzammil Arif Din Abdul ; Rabkin, Samuel D ; Kahramanian, Andranik ; Gorham, Joshua ; Rajan, Anant ; Wakimoto, Hiroko ; Turna Demir, Fatma ; Shimizu, Kazuhide ; Saad, Mohammad Ahsan ; Martuza, Robert L

Oncolytic viruses (OVs) have emerged as a clinical therapeutic modality potentially effective for cancers that evade conventional therapies, including central nervous system malignancies. Rationally designed combinatorial strategies can augment the efficacy of OVs by boosting tumor-selective cytotoxicity and modulating the tumor microenvironment (TME). Photodynamic therapy (PDT) of cancer not only mediates direct neoplastic cell death but also primes the TME to sensitize the tumor to secondary therapies, allowing for the combination of two potentially synergistic therapies with broader targets. Here, we created G47Δ-KR, clinical oncolytic herpes simplex virus G47Δ that expresses photosensitizer protein KillerRed (KR). Optical properties and cytotoxic effects of G47Δ-KR infection followed by amber LED illumination (peak wavelength: 585-595 nm) were examined in human glioblastoma (GBM) and malignant meningioma (MM) models in vitro. G47Δ-KR infection of tumor cells mediated KR expression that was activated by LED and produced reactive oxygen species, leading to cell death that was more robust than G47Δ-KR without light. In vivo, we tested photodynamic-oncolytic virus (PD-OV) therapy employing intratumoral injection of G47Δ-KR followed by laser light tumor irradiation (wavelength: 585 nm) in GBM and MM xenografts. PD-OV therapy was feasible in these models and resulted in potent anti-tumor effects that were superior to G47Δ-KR alone (without laser light) or laser light alone. RNA sequencing analysis of post-treatment tumor samples revealed PD-OV therapy-induced increases in TME infiltration of variable immune cell types. This study thus demonstrated the proof-of-concept that G47Δ-KR enables PD-OV therapy for neuro-oncological malignancies and warrants further research to advance potential clinical translation.

01 Sep 2023·Molecular therapy oncolytics

Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models

Article

Author: Inoue, Kosuke ; Todo, Tomoki ; Ito, Hirotaka ; Iwai, Miwako ; Mori, Yoshiyuki ; Tanaka, Minoru

A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without "hemilateral" resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47Δ therapy even when the resection area was narrowed to "partial," providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47Δ therapy caused increased number of tumor-infiltrating CD8⁺ and CD4⁺ cells, increased F4/80⁺ cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47Δ is useful for preventing local recurrence after tongue cancer surgery.

News (Medical) associated with Teserpaturev

09 Dec 2022

·www.biospace.com

DELYTACT The Latest Entrant In The Oncolytic Virus Therapy Market

One of the biggest threats to human health and life has always been cancer, and as instances rise each year, so do the financial and emotional burdens placed on patients and their families. While conventional treatment methods have been helpful in improving the patients’ survival and quality of life, little effect has been seen in patients with advanced forms of cancer, generating the need for new approaches for cancer management. In the last six decades, the discovery of oncolytic viruses has changed the research paradigm for cancer therapy and has emerged as one of the newest strategies for cancer management. The approval of three oncolytic viruses has further helped in grabbing the attention of pharmaceutical companies and researchers alike, which has been the main driver in promoting their growth. Global Oncolytic Virus Immunotherapy Market and Clinical Trials Insight 2028 Report Overview: Global Oncolytic Virus Immunotherapy Therapy Market Overview Global Oncolytic Virus Immunotherapy Therapy Market Opportunity: > USD 1 Billion By 2028 Insight On More Than 180 Oncolytic Virus Immunotherapies In Clinical Trials Patent Information On More Than 60 Therapies in Clinical Trials IMLYGIC, Oncorine, Delytact: Availability, Dosage and Price Analysis Oncolytic Virus Immunotherapy Clinical Pipeline By Country, Phase, Indication, Organization, Patient Segment Oncolytic Virus Immunotherapy Application By 10 Cancer Recent Strategic Partnerships, Collaborations, Mergers and Acquisitions Download Report: Oncolytic viruses, naturally or through genetic modifications, have the capacity to proliferate in cancer cells. The modality has been studied extensively in several types of cancer, and some of these OVs have also gained approval by regulatory bodies. Globally, Oncorine was the first oncolytic virus to be granted approval by a regulatory authority. It was approved in China in 2005 for the treatment of head and neck cancer. This was followed by the approval of Imlygic for treating melanoma by the FDA and EMA and is the only OV to have those approvals. More recently, Delytact received a conditional approval by Japan’s drug approval authority in June, 2021. The drug was given approval for the treatment of malignant glioma, which was a big milestone because no other OV has gained approval for brain cancer, demonstrating that the blood-barrier crossing abilities of these viruses can be utilized for the treatment of cancers of the brain. Delytact was developed jointly by Daichii Sankyo and Professor Tomoki Todo of the University of Tokyo’s Institute of Medical Science. It is a herpes simplex virus type 1 (HSV-1) which has been mutated to replicate exclusively in cancer cells. Oncolytic virus selectively replicate in cancer cells until cell death occurs post which, antitumor antigens produced by the virus are released in the tumor environment which allows the immune system to attack cancer cells by identifying the cancer antigens. It was granted a Sakigake fast-track designation in 2016 which was followed by an orphan regenerative medical product designation for malignant glioma in July, 2017. It has been given a 7 years limited time approval by the PMDA under which the company has to verify the safety and efficacy of the drug in the next seven years, after which the drug can be fully approved in the market. This approval was based in the data from a single-arm phase II trial which showed that treatment with Delytact improved the chances of survival in patients with residual or recurrent glioblastoma previously treated with radiotherapy and chemotherapy with Temodar (temozolomide). Regardless of the approval being only for a limited time, approval of Delytact given hope to many patients suffering from gliomas and also to researchers and pharmaceutical companies having drugs for brain cancer under development. Candel Therapeutics, DNAtrix and Transgene are some other companies apart from Daichii Sankyo who have OVs against brain cancer in clinical trials. While all these clinical trials are in early stages, the pursuers are expecting optimistic results for their respective drugs and from the approval process based on the designations held by Delytact and the conditions of its approval. Oncolytic viruses have been a lot of attention lately, mostly by the approval of Amgen’s Imlygic, which is among the handful of major pharmaceutical companies working on oncolytic virotherapy. The commercial performance of all these drugs will further fuel the development activities and allow the entry of more drugs in the development pipeline and the market. Contact: Neeraj Chawla Kuick research Research Head +91-981410366 neeraj@kuickresearch.com

Orphan DrugClinical ResultFast TrackPhase 2Drug Approval

100 Deals associated with Teserpaturev

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Glioma	JP	Daiichi Sankyo Co., Ltd.	11 Jun 2021

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma	Phase 2	-	The University of Tokyo Hospital	-
Glioblastoma	Phase 2	-	Daiichi Sankyo Co., Ltd.	-
Prostatic Cancer	Phase 2	-	Daiichi Sankyo Co., Ltd.	-
Prostatic Cancer	Phase 2	-	The University of Tokyo Hospital	-
Mesothelioma	Phase 1	JP	University of Tokyo	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASGCT2016	Not Applicable	Brain Stem Glioma	-	G47Δ	jgtvfmqhve(dcpnfearfy) = vimfarvgrh dzhcryktjl (ezkhjfkmzw )	-	01 May 2016
ASGCT2012	Not Applicable	Triple Negative Breast Cancer MAPK \| mTOR	-	Rapamycin	glexpnhiqd(lwqktvqthg) = ikoooccogj zqsomourlp (pulusjfyea )	Positive	01 May 2012
				NV1066 + Rapamycin	glexpnhiqd(lwqktvqthg) = ffteuvwvfx zqsomourlp (pulusjfyea )
ASGCT2010	Not Applicable	Brain Stem Glioma O6-methylguanine methyltransferase (MGMT) gene	-	Temozolomide	zkviwkgrcr(zonpazpbly) = cuutxdtbnq hftcdmgfou (vcsxtqtlxd )	Positive	01 May 2010
				O6-Benzylguanine	zkviwkgrcr(zonpazpbly) = zlfhbpsayn hftcdmgfou (vcsxtqtlxd )
ASGCT2007	Not Applicable	Neuroblastoma	-	G47Δ + iDC	ddzinjkszn(tczpewmyhg) = combined therapy was accompanied by a nearly four-fold increase in N18-specific IFNγ producing cells compared to virus treatment alone qbtwhncmnz (ayutczuhpj ) View more	-	01 May 2007
				G47Δ alone
ASGCT2003	Not Applicable	Ovarian Cancer	-	Oncolytic Herpes Simplex Virus	dpogvwnqwj(wsamspwssr) = leading to a significantly increased tumor cell killing ability ifuelnfgij (zdtrcisdvp )	Positive	01 May 2003

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Teserpaturev

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation