Ad5-yCD/mutTKSR39rep-hIL12(Ad5-yCD/mutTKSR39rep-hIL12) - 药物靶点：IL-12 x thymidine kinase_在研适应症：多形性胶质母细胞瘤，脑恶性胶质瘤，复发性前列腺癌_专利_临床

概要

基本信息

药物类型

溶瘤病毒

别名

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

靶点

IL-12 x thymidine kinase

作用机制

IL-12调节剂(白细胞介素-12复合体调节剂)、thymidine kinase调节剂(胸苷激酶调节剂)

治疗领域

肿瘤神经系统疾病泌尿生殖系统疾病+ [1]

在研适应症

多形性胶质母细胞瘤脑恶性胶质瘤复发性前列腺癌

非在研适应症

胰腺继发性恶性肿瘤

原研机构

Henry Ford Health System

在研机构

Henry Ford Health System

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

4

项与 Ad5-yCD/mutTKSR39rep-hIL12 相关的临床试验

NCT05686798 / Recruiting临床1期IIT

Phase I Study of Replication-Competent Adenovirus-Mediated Double Suicide Gene Therapy With Stereotactic Radiosurgery in Patients With Recurrent or Progressive High Grade Astrocytomas

The primary goal of this Phase I study is to determine the maximum tolerated dose of oncolytic adenovirus mediated double suicide-gene therapy in combination with fractionated stereotactic radiosurgery in patients with recurrent high-grade astrocytoma undergoing resection.

开始日期2022-11-29

申办/合作机构

Henry Ford Health System

NCT03281382 / Completed临床1期IIT

PHASE 1 TRIAL OF ONCOLYTIC ADENOVIRUS-MEDIATED CYTOTOXIC AND IL-12 GENE THERAPY IN COMBINATION WITH CHEMOTHERAPY FOR THE TREATMENT OF METASTATIC PANCREATIC CANCER

This phase 1 trial will investigate the toxicity of combining interleukin 12 gene therapy with standard chemotherapy in metastatic pancreatic cancer.

开始日期2017-07-01

申办/合作机构

Henry Ford Health System

NCT03029871 / Withdrawn临床1期IIT

Phase 1 Trial of Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Combination With Stereotactic Body Radiation Therapy (SBRT) in Clinical Stage 1/11A (T1A-T2B) Non-Small Cell Lung Cancer

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.

开始日期2017-01-13

申办/合作机构

Henry Ford Health System

100 项与 Ad5-yCD/mutTKSR39rep-hIL12 相关的临床结果

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100 项与 Ad5-yCD/mutTKSR39rep-hIL12 相关的转化医学

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100 项与 Ad5-yCD/mutTKSR39rep-hIL12 相关的专利（医药）

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3

项与 Ad5-yCD/mutTKSR39rep-hIL12 相关的文献（医药）

2023-01-01·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

作者: Brown, Stephen L ; Ali, Haythem ; Li, Pin ; Freytag, Svend O ; Movsas, Benjamin ; Siddiqui, Farzan ; Peabody, James ; Stricker, Hans ; Nyati, Shyam ; Barton, Kenneth N ; 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.

2021-03-01·Molecular Therapy - Oncolytics2区 · 医学

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

2区 · 医学

ArticleOA

作者: Ajlouni, Munther ; Movsas, Benjamin ; Zhang, Yingshu ; 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.

2013-12-01·Gene Therapy3区 · 医学

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

3区 · 医学

Article

作者: 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 项与 Ad5-yCD/mutTKSR39rep-hIL12 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
多形性胶质母细胞瘤	临床1期	美国	Henry Ford Health System	2022-11-29
脑恶性胶质瘤	临床1期	美国	Henry Ford Health System	2022-11-29
复发性前列腺癌	临床1期	美国	Henry Ford Health System	2015-08-01
胰腺继发性恶性肿瘤	临床前	美国	Henry Ford Health System	2017-07-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2023 人工标引	临床1期	复发性前列腺癌	15	Ad5-yCD/mutTKSR39rep-hIL-12+5-fluorocytosine+Valganciclovir	(範壓鹹蓋網醖壓壓艱顧) = 製醖廠蓋選憲範憲願顧憲顧醖鹹膚齋淵顧顧鑰 (醖糧選範鬱製淵網觸壓 ) 更多	积极	2023-04-14
NCT03281382 (Pubmed \| Mol Ther Oncolytics) 人工标引	临床1期	胰腺继发性恶性肿瘤	12	Flucytosine+Ad5-yCD/mutTKSR39 rep-hIL-12	(簾製製積積廠鹹構窪構) = ~94% of the 121 events were grade 1/2 requiring no medical intervention 壓獵遞醖簾獵範蓋醖製 (鹹遞獵網憲獵網夢淵艱 )	积极	2020-12-03