Delving into the Latest Updates on Ad-TD-nslL12 with Synapse

Overview

Basic Info

Drug Type

Oncolytic virus

Synonyms-

Target

IL-12

Mechanism

IL-12 modulators(Interleukin-12 modulators)

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases+ [3]

Active Indication

Diffuse Intrinsic Pontine GliomaRecurrent GlioblastomaColorectal Cancer+ [3]

Inactive Indication-

Originator Organization-

Active Organization

Zhengzhou University

Capital University of Medical Sciences

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 9145

Sequence Code 138947linker

Sequence Code 13225258

Sequence Code 13225263

Managing malignant brain tumors remains a significant therapeutic hurdle that necessitates further research to comprehend their treatment potential fully. Oncolytic viruses (OVs) offer many opportunities for predicting and combating tumors through several mechanisms, with both preclinical and clinical studies demonstrating potential. OV therapy has emerged as a potent and effective method with a dual mechanism. Developing innovative and effective strategies for virus transduction, coupled with immune checkpoint inhibitors or chemotherapy drugs, strengthens this new technique. Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors.

01 Jan 2024·Life sciences

Oncolytic virus Ad-TD-nsIL-12 inhibits glioma growth and reprograms the tumor immune microenvironment

Article

Author: Guo, Yuduo ; Wang, Yaohe ; Ning, Weihai ; Qu, Yanming ; Zhao, Chao ; Wang, Jun ; Wang, Shengdian ; Chen, Yujia ; Li, Shenglun ; Zhang, Hongwei ; Zhang, Mingshan ; Xu, Jiacheng ; Wang, Pengju

AIMS:

Gliomas are the most common central nervous system malignancies, with limited therapeutic options and poor prognosis, which are primarily attributed to the "immune desert" microenvironment. Previously, we constructed a three-gene-deleted oncolytic adenovirus (Ad-TD) loaded with non-secreting interleukin-12 (nsIL-12), which could be amplified in tumor cells and induce immunity to suppress tumors. However, the effects of this oncolytic virus on gliomas and their immune microenvironment remain unclear. There is an urgent need for further research.

MATERIALS AND METHODS:

We constructed a Syrian hamster brain tumor model and demonstrated the efficacy and mechanism of the novel oncolytic virus in treating brain tumors through a series of in vitro and in vivo experiments. We investigated the efficacy and safety (the number of hamsters in each group is either 5 or 10) of the oncolytic virus treatment in Syrian hamsters using a virus-treated group, a control virus-treated group, and a blank control group.

KEY FINDINGS:

In vitro assays showed that Ad-TD-nsIL-12 could specifically proliferate in brain tumor cells which induce tumor cell apoptosis and intracellular expression of interleukin (IL)-12. Moreover, in vivo experiments demonstrated that Ad-TD-nsIL-12 could effectively inhibit the progression of brain tumors and prolong survival. Ad-TD-nsIL-12 significantly enhanced T-cell infiltration in the brain tumor microenvironment.

SIGNIFICANCE:

Ad-TD-nsIL-12 can inhibit glioma progression and increase T-cell infiltration in the tumor tissue, particularly infiltration by cytotoxic T cells (CD8+). Ad-TD-nsIL-12 can amplify and produce IL-12, inducing anti-glioma immune responses to inhibit tumor progression.

03 Oct 2023·Expert opinion on biological therapy

Oncolytic virotherapies for pediatric tumors

Review

Author: Atchley, Travis J ; Johnston, James M ; Laskay, Nicholas Mb ; Estevez-Ordonez, Dagoberto ; Gross, Evan G ; Markert, James M ; Hamo, Mohammad A

INTRODUCTION:

Many pediatric patients with malignant tumors continue to suffer poor outcomes. The current standard of care includes maximum safe surgical resection followed by chemotherapy and radiation which may be associated with considerable long-term morbidity. The emergence of oncolytic virotherapy (OVT) may provide an alternative or adjuvant treatment for pediatric oncology patients.

AREAS COVERED:

We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). For each virus, we discuss the mechanism of tumor-specific replication and cytotoxicity as well as key findings of preclinical and clinical studies.

EXPERT OPINION:

Substantial progress has been made in the past 10 years regarding the clinical use of OVT. From our review, OVT has favorable safety profiles compared to chemotherapy and radiation treatment. However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future.

100 Deals associated with Ad-TD-nslL12

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse Intrinsic Pontine Glioma	Phase 1	CN	Capital University of Medical Sciences	04 Jan 2023
Recurrent Glioblastoma	Phase 1	CN	Capital University of Medical Sciences	27 Apr 2020
Colorectal Cancer	Preclinical	CN	Zhengzhou University	09 Nov 2017
Ovarian Cancer	Preclinical	CN	Zhengzhou University	09 Nov 2017
Pancreatic Cancer	Preclinical	CN	Zhengzhou University	09 Nov 2017
Stomach Cancer	Preclinical	CN	Zhengzhou University	09 Nov 2017