As part of oncolytic virotherapy to treat cancer, oncolytic viruses (OVs) can selectively infect tumor cells to promote oncolysis of cancer cells, local immunological reactions, and systemic antitumor immunity with minimal toxicity to normal tissues. The immunostimulatory properties of OVs provide enormous benefits for the treatment of cancer. A variety of OVs, including genetically engineered and natural viruses, have shown promise in preclinical models and clinical studies. In 2005, the China Food and Drug Administration approved its first OV drug, Oncorine (H101), for treatment of advanced head and neck cancer. To explore new treatment strategies, >200 recombinant or natural OVs are undergoing in-depth investigation in China, and >250 oncolytic virotherapy-related reports from the OV community in China have been published in the past 5 years. These studies investigated a variety of exogenous genes and combination therapeutic strategies to enhance the treatment effects of OVs. To date, five clinical trials covering four OV agents (Oncorine, OrienX010, KH901, and H103) are ongoing, and additional OV agents are awaiting approval for clinical trials in China. Overall, this research emphasizes that combination therapy, especially tumor immunotherapy coupled with effective system administration strategies, can promote the development of oncolytic virotherapies. This article focuses on studies that were carried out in China in order to give an overview of the past, present, and future of oncolytic virotherapy in China.

2012-06-01·Current pharmaceutical biotechnology4区 · 医学

Clinical Development of Oncolytic Viruses in China

4区 · 医学

Review

作者: Liang, Min

The oncolytic virus, being a promising new therapeutic strategy for cancer, has inspired a wave of recent clinical research and development in China. The first commercialized oncolytic virus, Oncorine, was approved by Chinese SFDA in November 2005 for nasopharyngeal carcinoma combined with chemotherapy. Since then, a number of oncolytic viruses have been moved into clinical trials. Among these are the armed oncolytic adenoviruses such as H103 (expressing the heat shock protein) currently has finished phase I trial, and KH901 (expressing GM-CSF) now launched in phase II trial In this review, we will discuss the current status of ongoing oncolytic virus projects being conducted at various clinical stages in China, including the preliminary market response for Oncorine after it was launched into the Chinese market in 2006.

2012-01-01·Frontiers in bioscience (Elite edition)

Adenovirus KH901 promotes 5-FU antitumor efficacy and S phase in LoVo cells

Article

作者: X. G. Yin ; Jin Li ; Wei Peng ; L. Z. Cheng ; J. F. Xu

A combination of oncolytic and chemotherapeutic agents has been used to kill cancer cells. However, the effect of oncolytic adenoviruses on the cell cycle remains to be determined. Cytotoxicity assays were performed to determine cell death in cells treated with 5-fluorouracil (5-FU) alone or in combination with the oncolytic adenovirus KH901. Dynamic changes in the cell cycle, cell proliferation, and apoptosis-related proteins including p-AKT, Bcl-2, Bax, and caspase 3 were investigated after treatment with 5-FU with or without KH901. A higher proportion of S-phase cells were observed after treatment with KH901 and 5-FU than with 5-FU alone. p-AKT, Bcl-2, and Bax expression was increased upon treatment with KH901, whereas the expression of caspase-3 was not induced upon treatment with KH901 with or without 5-FU. KH901 exhibited significant potential as an oncolytic adenovirus and increased cell death in combination with 5-FU in LoVo cells, as compared to 5-FU alone. In conclusion, KH901 stimulates LoVo cells to enter the S-phase by activation of p-AKT, which could partly explain its synergistic effect with 5-FU on LoVo cell cytotoxicity.

项与特异性溶瘤重组腺病毒 (成都康弘生物) 相关的新闻（医药）

2021-02-03

·药融云

2020Q1-Q3康柏西普销售额达7.65亿，第4个新适应症即将来袭！康弘药业能否凭借国际化布局，“牛”转乾坤

导语近期，康弘药业向国家药品监督管理局递交其自主研发的1类生物创新药康柏西普眼用注射液（商品名：朗沐）的新适应症上市申请，这是康柏西普眼用注射液在国内递交的第四个上市申请。康柏西普是新一代VEGF融合蛋白，是我国首个获得世界卫生组织国际通用名的拥有全自主知识产权的生物1类新药，于2013年获批用于治疗湿性年龄相关性黄斑变性（nAMD），2017年获批用于治疗继发于病理性近视脉络膜新生血管（pmCNV），2019年获批用于治疗糖尿病性黄斑水肿（DME）。 2015年至今，康弘药业整体股价呈下降趋势，康柏西普第四个适应症递交上市申请能否帮助康弘药业渡过低迷期？图片来源：东方财富网康柏西普眼用注射液正在美国进行全球多中心的3期临床试验，跟阿柏西普做头对头的湿性年龄相关性黄斑变性的3期临床研究，这也是国内第一个因为临床数据表现优秀直接进入美国3期临床的生物药，已有数据表明这两款药物临床效果相当，但康柏西普眼用注射液注射频率更低。后续康柏西普眼用注射液还将开展继发于病理性近视脉络膜新生血管和糖尿病性黄斑水肿的美国3期临床试验。审评概况申请事项：境内生产药品注册注册分类：治疗用生物制品2.2类受理号：CXSS2100012 申请内容：增加新适应症“继发于视网膜静脉阻塞（RVO）的黄斑水肿” 康弘药业研发管线目前康弘药业的在研药物中，2款处于临床二期，1款处于临床一期，2款处于临床前。康弘公司目前主要产品为眼科领域的康柏西普眼用注射液；神经系统领域的舒肝解郁胶囊、阿立哌唑口崩片、右佐匹克隆片、盐酸文拉法辛缓释片；消化领域的胆舒胶囊、枸橼酸莫沙必利分散片；以及其他领域的一清胶囊、感咳双清胶囊、渴络欣胶囊、玄麦甘桔胶囊、松龄血脉康胶囊。表1 康弘药业研发管线（截止2021年1月）数据来源：药融云全球药物研发数据库竞争格局康柏西普是继雷珠单抗、阿柏西普后全球上市的第三款用于眼科疾病的抗VEGF药物，其中阿柏西普和康柏西普同属于VEGFR-Fc融合蛋白。继发于视网膜静脉阻塞的黄斑水肿，首选抗VEGF药物治疗。在国内，目前获批治疗视网膜静脉阻塞的抗VEGF药物仅有雷珠单抗。康柏西普眼用注射液关于湿性年龄相关性黄斑变性也已经在哥伦比亚进行3期临床试验，还在蒙古提交了上市申请。表2 康柏西普各在研适应症的全球研发现状（截止2021年1月）数据来源：药融云全球药物研发数据库雷珠单抗在全球已上市适应症有湿性年龄相关性黄斑变性、糖尿病性黄斑水肿、脉络膜新生血管、视网膜静脉阻塞、糖尿病性视网膜病变、早产儿视网膜病变。其中湿性年龄相关性黄斑变性、糖尿病性黄斑水肿、脉络膜新生血管、视网膜静脉阻塞已在我国上市。雷珠单抗和康柏西普眼用注射液的适应症基本一致，两个药物并驱争先。康柏西普眼用注射液注射频率是前三个月每月1针，之后每三个月1针，全年共6针，而雷珠单抗全年需要12针。如果康柏西普眼用注射液递交的第四个适应症上市申请获批，将进一步增加其市场竞争力。表3 雷珠单抗各在研适应症的全球研发现状（截止2021年1月）上下滑动查看更多数据来源：药融云全球药物研发数据库阿柏西普在全球已上市适应症青光眼、视网膜静脉阻塞、非增殖性糖尿病性视网膜病变、糖尿病性黄斑水肿、脉络膜新生血管、黄斑水肿、湿性年龄相关性黄斑变性、糖尿病性视网膜病变。在我国上市适应症只有糖尿病性黄斑水肿和湿性年龄相关性黄斑变性。表4 阿柏西普各在研适应症的全球研发现状（截止2021年1月）上下滑动查看更多数据来源：药融云全球药物研发数据库结语康柏西普由康弘药业原副总辞俞德超主导研发出来，俞德超在康弘药业主导研发了5款生物一类药。俞德超从康弘离职后，原计划于2019年上市的KH-901，一直处于临床二期。俞德超目前创办的信达生物也是风生水起，达成了与礼来制药多项协议（包含了新型双特异性肿瘤免疫治疗抗体）。有人比较担心俞德超的离开对康弘的影响比较大，但是康弘药业2020年大额募资，加码国际化。毫无疑问，康柏西普眼用注射液是康弘药业的核心产品。2014年到2019年，康柏西普眼用注射液的销售额逐年递增，直至2019年，销售额达到9亿元。2020年因为疫情和降价的影响，销售额有所下降。但随着2019年三个已获批适应症纳入医保以及第四个适应症递交上市申请，康柏西普眼用注射液的有望进一步打开市场，可以预见其销售额仍会增速，是未来公司持续成长的主要推动力。版权声明：本文转自药融云，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看