Phase I Clinical Trial of Endovenous Administration of Conditionally Replicative Adenovirus ICOVIR-5 in Patients With Locally Advanced or Metastatic Melanoma

The investigators will evaluate the safety of a single endovenous infusion of ICOVIR5 in adults with locally advanced and metastatic melanoma. ICOVIR5 consists in a conditionally replicative or oncolytic adenovirus.

开始日期2013-01-11

申办/合作机构

Institut Català d'Oncologia

100 项与 ICOVIR-5 相关的临床结果

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100 项与 ICOVIR-5 相关的转化医学

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100 项与 ICOVIR-5 相关的专利（医药）

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项与 ICOVIR-5 相关的文献（医药）

2024-09-01·Molecular Therapy: Oncology

Deletion of the RGD motif from the penton base in oncolytic adenoviruses enhances antitumor efficacy of combined CAR T cell therapy

Article

作者: Hidalgo, Laura ; Morales-Molina, Alvaro ; Garcia-Castro, Javier ; Garcia-Rodriguez, Patricia ; Rodriguez-Milla, Miguel Angel ; Alemany, Ramon

Oncolytic viruses often face challenges in achieving optimal antitumor immunity as standalone therapies. The penton base RGD-integrin interactions play a significant role in wild-type adenovirus-induced innate immune responses. To modify these responses, we present ISC301, a novel oncolytic adenovirus engineered by deleting the natural RGD motifs in the penton base while incorporating artificial RGD motifs in the fiber knobs. ISC301 demonstrated comparable in vitro infectivity, cytotoxic effects, and signaling profiles across various cell types to its parental ICOVIR-5, which retains the penton base RGD motif. In immunodeficient and immunocompetent mouse models, ISC301 exhibited similar in vivo antitumor efficacy to ICOVIR-5. However, ISC301 induced higher intratumoral inflammation through NF-κB activation, leading to increased levels of tumor-infiltrating leukocytes and higher proportion of cytotoxic CD8⁺ T cells. In addition, ISC301 elicits a heightened pro-inflammatory response in peripheral blood. Importantly, when combined with CAR T cell therapy, ISC301 exhibited superior antitumor efficacy, surpassing monotherapy outcomes. These findings emphasize the impact of adenoviral modifications on antitumor immune responses. The deletion of penton base RGD motifs enhances ISC301's pro-inflammatory profile and boosts CAR T cell therapy efficacy. This study enhances understanding of oncolytic virus engineering strategies, positioning ISC301 as a promising candidate for combined immunotherapeutic approaches in cancer treatment.

2021-02-01·Cancer Gene Therapy2区 · 医学

AKT and JUN are differentially activated in mesenchymal stem cells after infection with human and canine oncolytic adenoviruses

2区 · 医学

Article

作者: García-Castro, Javier ; Morales-Molina, Alvaro ; Perisé-Barrios, Ana Judith ; Cejalvo, Teresa ; Rodríguez-Milla, Miguel Ángel

There is increasing evidence about the use of oncolytic adenoviruses (Ads) as promising immunotherapy agents. We have previously demonstrated the clinical efficiency of mesenchymal stem cells (MSCs) infected with oncolytic Ads as an antitumoral immunotherapy (called Celyvir) in human and canine patients, using ICOVIR-5 or ICOCAV17 as human and canine oncolytic Ads, respectively. Considering the better clinical outcomes of canine patients, in this study we searched for differences in cellular responses of human and canine MSCs to Ad infection that may help understand the mechanisms leading to higher antitumor immune response. We found that infection of human and canine MSCs with ICOVIR-5 or ICOCAV17 did not activate the NF-κB pathway or the interferon regulatory factors IRF3 and IRF7. However, we observed differences in the profile of cytokines secretion, as infection of canine MSCs with ICOCAV17 resulted in lower secretion of several cytokines. Moreover, we showed that infection of human MSCs with ICOVIR-5 increased the phosphorylation of a number of proteins, including AKT and c-JUN. Finally, we demonstrated that differences in regulation of AKT and c-JUN in human and canine MSCs by ICOVIR-5 or ICOCAV17 are intrinsic to each virus. Our findings suggest that ICOCAV17 induces a more limited host response in canine MSCs, which may be related to a better clinical outcome. This result opens the possibility to develop new human oncolytic Ads with these specific properties. In addition, this improvement could be imitated by selecting specific human MSC on the basis of a limited host response after Ad infection.

2020-05-01·World Neurosurgery

Longitudinal Monitoring of Gd-DTPA Following Convection Enhanced Delivery in the Brainstem

作者: Mark M. Souweidane ; Umberto Tosi

BACKGROUNDConvection-enhanced delivery (CED) has been introduced into contemporary therapeutic strategies for incurable brain neoplasms as diffuse intrinsic pontine glioma. Therapeutic benefit in part is predictably dependent on drug distribution within tumors. However, therapeutics can rarely be detected through conventional imaging techniques. Coinfusion of the tracer gadolinium-diethylenetriaminepentacetate (Gd-DTPA) has been advocated to monitor drug distributive features including volume, tumor coverage, and efflux during and after administration. The kinetics of Gd-DTPA are unclear as longitudinal magnetic resonance imaging is rarely performed. Understanding these changes would have important implications related to the timing of diagnostic imaging and reliance on tracers as surrogates of pharmacokinetic drug monitoring.CASE DESCRIPTIONThe behavior of Gd-DTPA as a surrogate is presented in a time-dependent fashion as measured by repeated magnetic resonance imaging based on the case of a child with recurrent diffuse intrinsic pontine glioma treated with an oncolytic virus (ICOVIR-5) delivered by CED with coinfused Gd-DTPA (1 mM, for a volume of 2000 μL). Initial Vd/Vi was 1.46. Gd-DTPA was observed up to 18 hours post CED but not thereafter.CONCLUSIONSThis longitudinal imaging assessment provides a rare opportunity to better characterize the kinetics of surrogate tracers delivered by CED to the brainstem, highlighting the importance of immediate and longitudinal monitoring.

100 项与 ICOVIR-5 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
黑色素瘤	临床1期	-	Institut d'Investigació Biomèdica de Bellvitge	-
局部晚期黑色素瘤	药物发现	西班牙	Institut Català d'Oncologia	2013-01-11
转移性黑色素瘤	药物发现	西班牙	Institut Català d'Oncologia	2013-01-11