Delving into the Latest Updates on Ad5-yCD/mutTK(SR39)rep-ADP with Synapse

This is a randomized, controlled trial that will test the hypothesis that replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IRMT)will improve freedom from failure (FFF) relative to 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile.

Start Date01 Dec 2007

Sponsor / Collaborator

Henry Ford Health System

NCT00415454 / TerminatedPhase 1IIT

Phase I Study Combining Replication-Competent Adenovirus-Mediated Suicide Gene Therapy With Chemoradiotherapy for the Treatment of Non-Metastatic Pancreatic Adenocarcinoma

The primary purpose of this phase I study is to determine the safety of combining replication-competent adenovirus-mediated suicide gene therapy with chemoradiotherapy in patients with non-metastatic pancreatic cancer.

Start Date01 Nov 2006

Sponsor / Collaborator

Henry Ford Health System

100 Clinical Results associated with Ad5-yCD/mutTK(SR39)rep-ADP

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100 Translational Medicine associated with Ad5-yCD/mutTK(SR39)rep-ADP

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100 Patents (Medical) associated with Ad5-yCD/mutTK(SR39)rep-ADP

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13

Literatures (Medical) associated with Ad5-yCD/mutTK(SR39)rep-ADP

01 Jan 2015·Molecular Therapy - OncolyticsQ2 · MEDICINE

Preclinical toxicology of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy for prostate cancer

Q2 · MEDICINE

ArticleOA

Author: Freytag, Svend O ; Zhang, Yingshu ; Siddiqui, Farzan

The purpose of this study was to examine the toxicity of combining oncolytic adenovirus-mediated cytotoxic and interleukin 12 (IL-12) gene therapy in a preclinical model to support future phase 1 trials. One hundred and twenty C57BL/6 male mice received an intraprostatic injection of saline (n = 24) or an oncolytic adenovirus (Ad5-yCD/mutTK_SR39rep-mIL12) expressing two suicide genes and mouse IL-12 (n = 96). The adenovirus was administered at three dose levels (1.3 × 10⁶, 1.3 × 10⁷, 1.3 × 10⁸ vp/kg) followed by 2 weeks of 5-flurocytosine (5-FC) and gancliclovir (GCV) prodrug therapy. There were no premature deaths. Daily observations of animals did not reveal any obvious clinical problems throughout the 78-day in-life phase of the study. Animals in the highest adenovirus dose group exhibited lymphopenia and transaminitis on day 3, both of which resolved by day 17. Except for mild inflammation of the prostate and seminal vesicles, histopathology of major organs was largely unremarkable. IL-12 and interferon-gamma levels in prostate and serum peaked on day 3 and were either undetectable or returned to baseline levels by day 17. No adenoviral DNA was detected in serum in any group at any time point. The results demonstrate that local administration of an oncolytic adenovirus expressing two suicide genes and IL-12 is well tolerated and support moving this investigational approach into human trials.

01 Jul 2011·Molecular TherapyQ1 · MEDICINE

Feasibility of Adenovirus-Mediated hNIS Gene Transfer and 131I Radioiodine Therapy as a Definitive Treatment for Localized Prostate Cancer

Q1 · MEDICINE

Article

Author: Yingshu Zhang ; Svend O Freytag ; Kenneth N Barton ; Jan Pegg ; Kastytis C Karvelis ; Mei Lu ; Hans Stricker ; Jingfang Cheng ; Mohamed A Elshaikh ; Benjamin Movsas

We have developed a replication-competent adenovirus (Ad5-yCD/mutTK(SR39)rep-hNIS) armed with two suicide genes and the human sodium iodide symporter (hNIS) gene. In this context, hNIS can be used as a reporter gene in conjunction with nuclear imaging and as a potentially therapeutic gene when combined with (131)I radioiodine therapy. Here, we quantified the volume and magnitude of hNIS gene expression in the human prostate following injection of a high Ad5-yCD/mutTK(SR39)rep-hNIS dose using a standardized injection algorithm, and estimated the radiation dose that would be delivered to the prostate had men been administered (131)I with curative intent. Six men with clinically localized prostate cancer received an intraprostatic injection of Ad5-yCD/mutTK(SR39)rep-hNIS under transrectal ultrasound guidance. All men received 2 × 0.5 ml deposits (5 × 10(11) vp/deposit) in each of the four base and midgland sextants and 2 × 0.25 ml deposits (2.5 × 10(11) vp/deposit) in each of the two apex sextants for a total of 12 deposits (5 × 10(12) vp) in 5 ml. On multiple days after the adenovirus injection, men were administered sodium pertechnetate (Na(99m)TcO(4)) and hNIS gene expression in the prostate was quantified by single photon emission computed tomography (SPECT). hNIS gene expression was detected in the prostate of six of six (100%) men. On average, 45% (range 18-83%) of the prostate volume was covered with gene expression. Had men been administered 200 mCi (131)I, we estimate that the mean absorbed dose to the prostate would be 7.2 ± 4.8 Gy (range 2.1-13.3 Gy), well below that needed to sterilize the prostate. We discuss the obstacles that must be overcome before adenovirus-mediated hNIS gene transfer and (131)I radioiodine therapy can be used as a definitive treatment for localized prostate cancer.

01 Apr 2011·Molecular TherapyQ1 · MEDICINE

Sodium Iodide Symporter SPECT Imaging of a Patient Treated With Oncolytic Adenovirus Ad5/3-Δ24-hNIS

Q1 · MEDICINE

Letter

Author: Timo Kiljunen ; Leena Laasonen ; Jarmo Haukka ; Sophie Escutenaire ; Lotta Kangasniemi ; Aki Kangasmäki ; Maria Rajecki ; Sari Pesonen ; Akseli Hemminki ; Timo Joensuu ; Tanja Hakkarainen ; Kalevi Kairemo ; Ari Ristimäki

Because of the lack of curative treatment options for most advanced cancers, innovative and exptl. strategies are being developed.One promising therapeutic approach is the delivery of human sodium iodide symporter (hNIS) with oncolytic viruses.HNIS provides the dual utility of therapy and imaging of virus distribution with radionuclides such as iodides or technetium.Although therapy is the ultimate goal, imaging of the virus is also critical because all available biodistribution information concerning oncolytic viruses is currently based on animal models, which may not be fully representative for species-specific viruses such as human adenovirus.We believe our experience with Ad5/3-Δ24-hNIS in comparison with the report on Ad5-yCD/mutTKSR₃₉rep-hNIS reveals several important aspects in virus design.First, low oncolytic potency may be useful for expression of transgene products located on the cell surface.Second, slower virus replication (e.g., in combination with replication-attenuating prodrugs) may allow for better imaging of membrane-associated proteins.In addition, high levels of early transgene expression may be preferable over protracted replication-coupled transgene expression.Also, tumor-selective transgene expression may lead to less robust imaging results than expression in all transduced cells.Finally, the sensitivity of SPECT may require relatively high levels of transgene expression.Thus, Ad5-yCD/mutTKSR₃₉rep-hNIS may represent a useful agent for combining oncolytic virotherapy with prodrug-converting enzymes, imaging, and radionuclide therapy, whereas Ad5/3-Δ24-hNIS type viruses are more suitable for optimal oncolysis and expressing transgenes with systemic or paracrine rather than cell membrane-restricted effects.

100 Deals associated with Ad5-yCD/mutTK(SR39)rep-ADP

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Cancer	Phase 2	-	Henry Ford Health System	-
Pancreatic Cancer	Phase 2	-	New Gen Pharm, Inc.	-
Prostatic Cancer	Discovery	US	-	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00583492 (ReCAP, CTgov)	Phase 2	Prostatic Cancer	44	IMRT	wihmdlnrgi(ynetbwuuwy) = pykeklizhv tcrlklgtif (otamavdbcb, rajfhyiybn - qkjkrtmlfl) View more	-	17 Mar 2016