Delving into the Latest Updates on Contusugene ladenovec(Introgen Therapeutics, Inc.) with Synapse

Overview

Basic Info

Drug Type

Recombinant vector vaccine, Shared antigen vaccine, Therapeutic vaccine

Synonyms

Adenoviral p53, Contusugene ladenovec (USAN), Contusugene ladenovec Gendux

+ [6]

Target

p53

Action

modulators

Mechanism

p53 modulators(Tumor protein p53 modulators)

Therapeutic Areas

NeoplasmsCongenital DisordersEndocrinology and Metabolic Disease+ [6]

Active Indication-

Inactive Indication

Bladder CancerBronchiolo-Alveolar AdenocarcinomaEsophageal Carcinoma+ [8]

Originator Organization

Introgen Therapeutics, Inc.

Active Organization-

Inactive Organization

Eastern Cooperative Oncology GroupIntrogen Therapeutics, Inc.

License Organization-

Drug Highest PhaseDiscontinuedNDA/BLA

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 545434317

This phase I/II trial is studying the side effects and best dose of gene therapy and to see how well it works in preventing cancer in patients with premalignant carcinoma of the oral cavity or pharynx. Inserting the p53 gene into a person's tumor cells may improve the body's ability to kill the tumor cells

Start Date01 Jun 2003

Sponsor / Collaborator

National Cancer Institute

NCT00410865

/ TerminatedPhase 1IIT

Clinical Protocol for Wild Type p53 Gene Induction in Premalignancies of Squamous Epithelium of the Oral Cavity and Oral Pharynx Via an Adenoviral Vector [NCI Supplied Agent Ad-p53, (INGN 201) (Advexin®) NSC 683550, IND# 7135]

Primary Objectives:
To determine the maximum tolerated dose and transduction efficiency of adenoviral mediated wild type p53 gene transfer in premalignancies of the upper aerodigestive tract.
To determine the efficacy of single agent adenoviral mediated wild type p53 gene transfer in reversing oral premalignancies.

Start Date01 Jun 2003

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+2]

100 Clinical Results associated with Contusugene ladenovec(Introgen Therapeutics, Inc.)

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100 Translational Medicine associated with Contusugene ladenovec(Introgen Therapeutics, Inc.)

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100 Patents (Medical) associated with Contusugene ladenovec(Introgen Therapeutics, Inc.)

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112

Literatures (Medical) associated with Contusugene ladenovec(Introgen Therapeutics, Inc.)

01 Jun 2022·Cancer Gene TherapyQ2 · MEDICINE

Tumor suppressor immune gene therapy to reverse immunotherapy resistance

Q2 · MEDICINE

Article

Author: Chada, Sunil ; Talbott, Max ; Menander, Kerstin B ; Ahn, Hyo Min ; Jung, Bo-Kyeong ; Wiederhold, Dora ; Sellman, Beatha ; Sobol, Robert E ; Nemunaitis, John J ; Yun, Chae-Ok

AbstractBackgroundWhile immune checkpoint inhibitors are becoming a standard of care for multiple types of cancer, the majority of patients do not respond to this form of immunotherapy. New approaches are required to overcome resistance to immunotherapies.MethodsWe investigated the effects of adenoviral p53 (Ad-p53) gene therapy in combination with immune checkpoint inhibitors and selective IL2 or IL15 CD122/132 agonists in the aggressive B16F10 tumor model resistant to immunotherapies. To assess potential mechanisms of action, pre- and post- Ad-p53 treatment biopsies were evaluated for changes in gene-expression profiles by Nanostring IO 360 assays.ResultsThe substantial synergy of “triplet” Ad-p53 + CD122/132 + anti-PD-1 therapy resulted in potential curative effects associated with the complete tumor remissions of both the primary and contralateral tumors. Interestingly, contralateral tumors, which were not injected with Ad-p53 showed robust abscopal effects resulting in statistically significant decreases in tumor size and increased survival (p < 0.001). None of the monotherapies or doublet treatments induced the complete tumor regressions. Ad-p53 treatment increased interferon, CD8+ T cell, immuno-proteosome antigen presentation, and tumor inflammation gene signatures. Ad-p53 treatment also decreased immune-suppressive TGF-beta, beta-catenin, macrophage, and endothelium gene signatures, which may contribute to enhanced immune checkpoint inhibitor (CPI) efficacy. Unexpectedly, a number of previously unidentified, strongly p53 downregulated genes associated with stromal pathways and IL10 expression identified novel anticancer therapeutic applications.ConclusionsThese results imply the ability of Ad-p53 to induce efficacious local and systemic antitumor immune responses with the potential to reverse resistance to immune checkpoint inhibitor therapy when combined with CD122/132 agonists and immune checkpoint blockade. Our findings further imply that Ad-p53 has multiple complementary immune mechanisms of action, which support future clinical evaluation of triplet Ad-p53, CD122/132 agonist, and immune checkpoint inhibitor combination treatment.

01 Aug 2019·Pharmaceutical Medicine

Current Prospects of Molecular Therapeutics in Head and Neck Squamous Cell Carcinoma

Review

Author: Devaraja, K

Head and neck squamous cell carcinoma (HNSCC) has an estimated annual global death rate of approximately 300,000. Despite advances in surgical techniques, the advent of efficient radiation delivery methods, and the introduction of newer chemotherapeutic agents, the survival rate for HNSCC has alarmingly remained unchanged for the past 50 years. However, there have been some promising developments in this field recently. Tumor protein 53 (TP53)-based gene therapeutics such as Gendicine^® and Advexin^®, and oncolytic viral therapeutics such as ONYX-015 and H101 have shown encouraging results and are gaining momentum. Cetuximab, the first US Food and Drug Administration-approved targeted therapeutic in HNSCC, although had a promising run initially, failed to garner enough attention subsequently due to its poor results in locally advanced HNSCC. Currently, its major utility is in palliation of recurrent and/or metastatic HNSCC as a part of the EXTREME regimen alongside cisplatin/carboplatin and fluorouracil. Of late, immunotherapeutics are evolving rapidly in HNSCC by demonstrating satisfactory effectiveness and acceptable tolerance both in locally advanced and recurrent tumors, and both as monotherapy and in combination with other agents. Recent accelerated approval of two immune checkpoint receptor blockers, pembrolizumab and nivolumab, has rejuvenated enthusiasm among clinicians and researchers by opening up a new domain for targeted and co-targeted therapeutics. The interim results of many ongoing trials and the latest updates of previous landmark trials such as KEYNOTE and CheckMate show promising trends in this regard. Immunotherapeutic agents belonging to different classes, such as durvalumab, epacadostat, motolimod, and T4 immunotherapy, are all being investigated presently in various therapeutic roles. Human papilloma virus (HPV)-based vaccines are now understood to have both a preventive and therapeutic role in HNSCC. Phase I/II trials are underway evaluating the safety profile, tolerable limits, and therapeutic efficacy of several therapeutic vaccines against HPV-driven HNSCC. Similarly, co-targeting therapeutics and precision medicine concepts are exploring newer and effective options including individuating the therapy based on particular tumor's molecular makeup and so on, the results of which are expected to change the landscape of HNSCC.

01 Nov 2018·Laboratory InvestigationQ2 · MEDICINE

Wild-type p53-modulated autophagy and autophagic fibroblast apoptosis inhibit hypertrophic scar formation

Q2 · MEDICINE

Article

Author: Tao, Ke ; Guan, Hao ; Li, Yan ; Zhang, Jian ; Bai, Xiaozhi ; Shi, Jihong ; Li, Jun ; Wang, Xujie ; Zhang, Julei ; Xiao, Houan ; Hu, Dahai

Hypertrophic scarring is a serious fibrotic skin disease, and the abnormal activation of hypertrophic scar fibroblasts (HSFs) intensifies its pathogenesis. Our previous studies have demonstrated that the dysregulation of autophagy in HSFs is associated with fibrosis. However, knowledge regarding the regulation of HS fibrosis by p53-modulated autophagy is limited. Here, we investigated the effect of p53-modulated autophagy on HS fibrosis. The overexpression of wtp53 (Adp53) promoted autophagic capacity and inhibited collagen and α-SMA expression in HSFs. In contrast, LC3 (AdLC3) overexpression did not suppress Col 1, Col 3, or α-SMA expression, but LC3 (shLC3) knockdown downregulated collagen expression. Adp53-modulated autophagy altered Bcl-2 and Bcl-xL expression, but AdLC3 affected only Bcl-xL expression. Silencing Bcl-xL suppressed collagen expression, but autophagy was also inhibited. Flow cytometry showed that the silencing of Bcl-2 (sibcl-2), Bcl-xL (sibcl-xL), and Adp53 significantly increased apoptosis in the HSFs. Therefore, wtp53 inhibited fibrosis in the HSFs by modulating autophagic HSF apoptosis; moreover, the inhibition of autophagy by sibcl-xL had antifibrotic effects. In addition, treatment with Adp53, AdLC3, shLC3, sibcl-2, and sibcl-xL reduced scar formation in a rabbit ear scar model. These data confirm that wtp53-modulated autophagy and autophagic HSF apoptosis can serve as potential molecular targets for HS therapy.

100 Deals associated with Contusugene ladenovec(Introgen Therapeutics, Inc.)

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External Link

KEGG	Wiki	ATC	Drug Bank
D06577	-	-	DB05322

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Squamous Cell Carcinoma of the Head and Neck	NDA/BLA	United States	Introgen Therapeutics, Inc.	12 Jul 2002
Locally advanced breast cancer	NDA/BLA	United States	Introgen Therapeutics, Inc.	01 Feb 2002
Bladder Cancer	NDA/BLA	United States	-	-
Bladder Cancer	NDA/BLA	-	Introgen Therapeutics, Inc.	-
Esophageal Carcinoma	NDA/BLA	Japan	Introgen Therapeutics, Inc.	-
Head and Neck Neoplasms	NDA/BLA	European Union	-	-
Li-Fraumeni Syndrome	NDA/BLA	European Union	Introgen Therapeutics, Inc.	-
Non-Small Cell Lung Cancer	NDA/BLA	United States	Introgen Therapeutics, Inc.	-
Ovarian Cancer	NDA/BLA	United States	-	-
Ovarian Cancer	NDA/BLA	-	Introgen Therapeutics, Inc.	-