Delving into the Latest Updates on Ad5-yCD/mutTKSR39rep-hIL12 with Synapse

Overview

Basic Info

Drug Type

Oncolytic virus

Synonyms

Ad5-yCD/mutTKSR39rep-hIL12, Cytosine deaminase herpes simplex virus-1/thymidine kinase fusion gene therapy(Henry Ford Health System), Radiation-sensitising gene therapy

Target

IL-12 x thymidine kinase

Mechanism

IL-12 modulators(Interleukin-12 modulators), thymidine kinase modulators(Thymidine kinase modulators)

Therapeutic Areas

NeoplasmsNervous System DiseasesUrogenital Diseases+ [1]

Active Indication

Glioblastoma MultiformeMalignant glioma of brainRecurrent Prostate Carcinoma

Inactive Indication

Secondary malignant neoplasm of pancreas

Originator Organization

Henry Ford Health System

Active Organization

Henry Ford Health System

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in combination with SBRT in medically inoperable stage I/IIA (T1A - T2B) NSCLC. To accomplish this objective, 9 subjects will be enrolled in the study. We hypothesize that the combined treatment will demonstrate acceptable toxicity, and that it will be feasible to quantify adenovirus-mediated HSV-1 TK gene expression in the lung by PET. This phase 1 trial will lay the foundation for a follow-up phase 2 trial designed to examine efficacy.

Start Date13 Jan 2017

Sponsor / Collaborator

Henry Ford Health System

100 Clinical Results associated with Ad5-yCD/mutTKSR39rep-hIL12

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100 Translational Medicine associated with Ad5-yCD/mutTKSR39rep-hIL12

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100 Patents (Medical) associated with Ad5-yCD/mutTKSR39rep-hIL12

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3

Literatures (Medical) associated with Ad5-yCD/mutTKSR39rep-hIL12

01 Jan 2023·PloS one

A phase I clinical trial of oncolytic adenovirus mediated suicide and interleukin-12 gene therapy in patients with recurrent localized prostate adenocarcinoma.

Article

Author: Brown, Stephen L ; Ali, Haythem ; Li, Pin ; Freytag, Svend O ; Movsas, Benjamin ; Siddiqui, Farzan ; Barton, Kenneth N ; Stricker, Hans ; Nyati, Shyam ; Peabody, James ; Elshaikh, Mohamed ; Hwang, Clara

In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors.

01 Mar 2021·Molecular Therapy - OncolyticsQ2 · MEDICINE

Phase I trial of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy for the treatment of metastatic pancreatic cancer

Q2 · MEDICINE

ArticleOA

Author: Zhang, Yingshu ; Ajlouni, Munther ; Movsas, Benjamin ; Barton, Kenneth N ; Dobrosotskaya, Irina ; Khan, Gazala ; Siddiqui, Farzan ; Cheng, Jingfang ; Kwon, David ; Pompa, Robert ; Freytag, Svend O

The safety of oncolytic adenovirus-mediated suicide and interleukin-12 (IL 12) gene therapy was evaluated in metastatic pancreatic cancer patients. In this phase I study, a replication-competent adenovirus (Ad5-yCD/mutTK_SR39 rep-hIL-12) expressing yCD/mutTK_SR39 (yeast cytidine deaminase/mutant S39R HSV-1 thymidine kinase) and human IL-12 (IL 12) was injected into tumors of 12 subjects with metastatic pancreatic cancer (T2N0M1-T4N1M1) at escalating doses (1 × 10¹¹, 3 × 10¹¹, or 1 × 10¹² viral particles). Subjects received 5-fluorocytosine (5-FC) therapy for 7 days followed by chemotherapy (FOLFIRINOX or gemcitabine/albumin-bound paclitaxel) starting 21 days after adenovirus injection. The study endpoint was toxicity through day 21. Experimental endpoints included measurements of serum IL 12, interferon gamma (IFNG), and CXCL10 to assess immune system activation. Peripheral blood mononuclear cells and proliferation markers were analyzed by flow cytometry. Twelve patients received Ad5-yCD/mutTK_SR39 rep-hIL-12 and oral 5-FC. Approximately 94% of the 121 adverse events observed were grade 1/2 requiring no medical intervention. Ad5-yCD/mutTK_SR39 rep-hIL-12 DNA was detected in the blood of two patients. Elevated serum IL 12, IFNG, and CXCL10 levels were detected in 42%, 75%, and 92% of subjects, respectively. Analysis of immune cell populations indicated activation after Ad5-yCD/mutTK_SR39 rep-hIL-12 administration. The median survival of patients in the third cohort is 18.1 (range, 3.5-20.0) months. The study maximum tolerated dose (MTD) was not reached.

01 Dec 2013·Gene TherapyQ3 · MEDICINE

Efficacy of oncolytic adenovirus expressing suicide genes and interleukin-12 in preclinical model of prostate cancer

Q3 · MEDICINE

Article

Author: Y Zhang ; K N Barton ; S O Freytag

Oncolytic adenovirus-mediated suicide gene therapy has been shown to improve local tumor control in preclinical tumor models and in the clinic. Although local tumor control is important, for most human cancers, new therapies must also target metastatic disease if they are to have an impact on survival. Here, we test the hypothesis that adding cytokine gene therapy to our multimodal platform improves both local and metastatic tumor control in a preclinical model of prostate cancer. An oncolytic adenovirus (Ad5-yCD/mutTKSR39rep-mIL12) expressing two suicide genes and mouse interleukin-12 (IL-12) was generated. Relative to an adenovirus lacking IL-12 (Ad5-yCD/mutTKSR39rep), Ad5-yCD/mutTKSR39rep-mIL12 improved local and metastatic tumor control in the TRAMP-C2 prostate adenocarcinoma model, resulting in a significant increase in survival. Ad5-yCD/mutTKSR39rep-mIL12 resulted in high levels of IL-12 and interferon gamma in serum and tumor, increased natural killer (NK) and cytotoxic T-lymphocyte lytic activities, and the development of tumor-specific antitumor immunity. Immune cell depletion studies indicated that both the innate and adaptive arms of immunity were required for maximal Ad5-yCD/mutTKSR39rep-mIL12 activity. The results demonstrate that the addition of IL-12 significantly improves the efficacy of oncolytic adenovirus-mediated suicide gene therapy and provide the scientific basis for future trials targeting locally aggressive cancers.

100 Deals associated with Ad5-yCD/mutTKSR39rep-hIL12

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma Multiforme	Phase 1	US	Henry Ford Health System	29 Nov 2022
Malignant glioma of brain	Phase 1	US	Henry Ford Health System	29 Nov 2022
Recurrent Prostate Carcinoma	Phase 1	US	Henry Ford Health System	01 Aug 2015
Secondary malignant neoplasm of pancreas	Preclinical	US	Henry Ford Health System	01 Jul 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AACR2023 Manual	Phase 1	Recurrent Prostate Carcinoma	15	Ad5-yCD/mutTKSR39rep-hIL-12+5-fluorocytosine+Valganciclovir	(yhvgmnqcwo) = xpvjzhiyzf azoaxowvuf (zfrwozuzti ) View more	Positive	14 Apr 2023
NCT03281382 (Pubmed \| Mol Ther Oncolytics) Manual	Phase 1	Secondary malignant neoplasm of pancreas	12	Flucytosine+Ad5-yCD/mutTKSR39 rep-hIL-12	(artyhnkydc) = ~94% of the 121 events were grade 1/2 requiring no medical intervention fnphmvfrlj (cauaclrubd )	Positive	03 Dec 2020