AVA-201(AVA-201) - 在研适应症：口腔肿瘤，黏膜白斑_专利_临床

概要

基本信息

药物类型

腺相关病毒基因治疗

别名

AVA-201 - Avalon GloboCare、MSC-EV-miR-185、MSC-Exo-miR185

+ [2]

靶点-

作用机制

RNA干扰

治疗领域

肿瘤口颌疾病

在研适应症

口腔肿瘤黏膜白斑

非在研适应症-

原研机构

Avalon GloboCare Corp.

在研机构

Avalon GloboCare Corp.

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 AVA-201 相关的临床结果

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100 项与 AVA-201 相关的转化医学

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100 项与 AVA-201 相关的专利（医药）

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7

项与 AVA-201 相关的文献（医药）

2019-12-04·Artificial cells, nanomedicine, and biotechnology2区 · 工程技术

Delivery of mesenchymal stem cells-derived extracellular vesicles with enriched miR-185 inhibits progression of OPMD

2区 · 工程技术

ArticleOA

作者: Yin, Panpan ; Sun, Zheng ; Guan, Xiaobing ; Wang, Jiaqi ; Wang, Lin ; Wang, Yuanyuan ; Zhou, Yu

Oral leukoplakia is one of the most common oral potentially malignant disorders (OPMDs) and its malignant transformation to oral cancer is highly associated with chronic inflammation. Extracellular vesicles (EVs) or exosome-delivered microRNAs modulate inflammatory responses and alleviate irritations that predisposes to cancer. We previously reported that microRNA-185 (miR-185) was significantly decreased in the buccal tissue of patients with oral cancer. In this study, we utilized genetically modified mesenchymal stem cells (MSCs) derived EVs with high expression of miR-185 to pasted MSC-EV-miR-185 on buccal lesions in dimethylbenzanthracene (DMBA) induced OPMD model. We found that treatment with MSC-EV-miR-185 remarkably attenuated inflammation severity and significantly decreased the incidence and the number of dysplasia in the OPMD tissue. Immunohistochemistry showed significantly decreased expression of proliferation marker PCNA and angiogenic marker CD31 in the lesion treated with MSC-EV-miR-185. Furthermore, miR-185 specifically targeted Akt genes by promoting activation of the apoptotic pathway, confirmed by the increased levels of activated caspase-3 and 9. In conclusion, genetically modified MSC-derived EVs enriched with miR-185 alleviate inflammatory response, inhibit cell proliferation and angiogenesis, and induce cell apoptosis, suggesting that their potential role as a novel therapeutic option for OPMD.

2019-08-01·American journal of ophthalmology2区 · 医学

Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration

2区 · 医学

Article

作者: Cora M. Pierce ; Aaron L. Magno ; Mark S. Blumenkranz ; Elizabeth P. Rakoczy ; Chooi May Lai ; Mariapia A. Degli-Esposti ; Ian J. Constable

PURPOSE:

To assess the safety and the 3-year results of combined phase 1 and 2a randomized controlled trials of rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration.

DESIGN:

Phase 1/2a clinical trial.

METHODS:

Patients were prospectively randomized into control (n = 13) and GT (n = 24) groups. GT patients received 1X10¹¹vg rAAV.sFLT-1 and were seen every month for 1 year then as needed every 1 to 2 months. They were given retreatment anti-vascular endothelial growth factor injections according to predetermined criteria. At 12 months, GT patients were divided into 2 groups: HD-1 (n = 14), requiring <2, and HD-2 (n = 10), requiring >2 retreatments.

RESULTS:

Between 1 year and 3 years there were 3 adverse events (AEs) and 33 serious AEs reported. Of these, 15 occurred in the 13 control subjects and 21 in the 24 GT patients. Except for 1 case of transient choroiditis in a control patient, serious AEs were deemed to be unrelated to the study. Control patients received a median of 7.0 retreatments and lost a median of 7.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, HD-1 patients received a median of 2.5 retreatments and lost a median of 4.0 ETDRS letters, and HD-2 patients received a median of 11.0 retreatments and lost a median of 7.0 ETDRS letters over 3 years. Center point thickness fluctuated. Thirty-three percent of control subjects, 44% of HD-2 patients, and 51% of HD-1 patients showed maintenance of baseline visual acuity. Four HD-1 patients (34%) maintained significant visual improvement at 3 years. None of these observations were statistically significant.

CONCLUSIONS:

Given the small number of patients, this study was unable to unequivocally confirm the existence of a biologic efficacy signal; however, it confirmed that rAAV.sFLT-1 gene delivery was well tolerated among the elderly.

2017-05-01·American journal of ophthalmology2区 · 医学

Gene Therapy in Neovascular Age-related Macular Degeneration: Three-Year Follow-up of a Phase 1 Randomized Dose Escalation Trial

2区 · 医学

Article

作者: Aaron L. Magno ; Ian J. Constable ; Samuel B. Barone ; Mark S. Blumenkranz ; Steven D. Schwartz ; Chooi May Lai ; Martyn A. French ; Mariapia A. Degli-Esposti ; Elizabeth P. Rakoczy

PURPOSE:

To assess the safety of rAAV.sFlt-1 subretinal injection in neovascular age-related macular degeneration (wet AMD) over 36 months.

DESIGN:

Phase 1 dose escalation trial.

METHODS:

Eight subjects with advanced, treatment-experienced wet AMD were randomly assigned (3:1) to treatment and non-gene therapy control groups. Eligible subjects were ≥65 years, had wet AMD, and had best-corrected visual acuity (BCVA) 10/200 to 20/80 in the study eye and 20/200 or better in the other eye. Three of the treatment group subjects received low-dose (1 × 10¹⁰ vector genomes) and 3 high-dose (1 × 10¹¹ vector genomes) rAAV.sFLT-1 via subretinal injection. Study monitoring was monthly to the primary endpoint at month 12 and then protocol-driven follow-up study visits were conducted at months 18 and 36. All subjects received intravitreal ranibizumab at baseline and at week 4, and retreatment injections at subsequent visits based on prespecified criteria for active wet AMD. The primary endpoint was ocular and systemic safety, but exploratory data including BCVA, retinal center point thickness, and the number of ranibizumab retreatments at and between study visits were also analyzed.

RESULTS:

Six of the 8 subjects completed the 36-month study. Subretinal injection with pars plana vitrectomy was well tolerated in this cohort. No ocular or systemic safety signals were observed during the long-term follow-up period. Exploratory data analysis suggests stability of wet AMD over the 36-month period.

CONCLUSIONS:

Subretinal delivery of rAAV.sFLT-1 was well tolerated and demonstrated a favourable safety profile through month 36. Thus, rAAV.sFLT-1 could be safely considered for future evaluation in the treatment of wet AMD.

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