Keratinocyte Growth Factor (KGF): Clinical Applications

角质形成细胞生长因子 (KGF)：临床应用

• 批准号: 7965533
• 负责人: Jeffrey Rubin
• 金额: $ 1.9万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7965533
• 关键词: Alternative Splicing; Autologous; Biological; Cell Surface Receptors; Clinical; Clinical Trials; Cloning; Communities; Dose; Epithelial Cells; Epithelium; Exposure to; FDA approved; FGF7 gene; Generic Drugs; Growth Factor; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Hematologic Neoplasms; Incidence; Knowledge; Legal patent; Licensing; Marketing; Molecular Cloning; Names; Patients; Peripheral Stem Cell Transplantation; Phase III Clinical Trials; Postdoctoral Fellow; Protein Isoforms; Protein Tyrosine Kinase; Radiation therapy; Recombinants; Report (document); Research; Rights; Scientist; Series; Specificity; Squamous Cell; Therapeutic; Trademark; Work; base; cancer therapy; chemotherapy; clinical application; dissemination research; drug development; irradiation; keratinocyte growth factor; oral mucositis; pre-clinical research; safety testing; therapeutic development

I purified keratinocyte growth factor (KGF, also known as FGF7) as a postdoctoral fellow in the late 1980s, and have been involved in its research ever since. Milestones achieved in our lab included molecular cloning and recombinant expression of the growth factor, characterization of its predominant epithelial cell specificity, identification and cloning of its tyrosine kinase cell surface receptors, FGFR2IIIb isoforms that arise from alternative splicing primarily confined to epithelial cells. Several collaborative studies broadened our understanding of its biological activities, including the first report documenting its remarkable cytoprotective effects. Amgen, Inc. licensed patent rights to KGF for the development of therapeutic products. Preclinical research performed by Amgen scientists and associates provided further evidence that KGF had therapeutic potential in reducing damage to epithelia following exposure to chemo/radiotherapy. A series of clinical trials tested the safety and efficacy of KGF in decreasing the incidence and duration of severe oral mucositis in patients receiving intensive cancer therapy. This work culminated in a successful phase 3 trial involving patients with hematologic malignancies who received high dose chemo/radiotherapy prior to autologous peripheral blood progenitor cell transplantation. Based on these results, the FDA approved use of KGF in this clinical context and the product went on the market in January2005 (trademark name is Kepivance, generic name is palifermin). Subsequent results from two phase 3 clinical trials suggest that palifermin would be safe and effective for a similar indication in patients who receive intensive chemotherapy and irradiation to treat head/neck squamous cell carcinoma.

我作为博士后纯化角质细胞生长因子（KGF，也称为FGF 7） 他在20世纪80年代末成为一名研究员，并从那时起一直参与其研究。里程碑 本实验室的主要研究成果包括： 因子，表征其主要的上皮细胞特异性，鉴定和 克隆其酪氨酸激酶细胞表面受体FGFR 2 IIIb同种型， 选择性剪接主要局限于上皮细胞。几项合作研究 扩大了我们对其生物活性的了解，包括第一份报告， 记录了它显著的细胞保护作用。Amgen公司KGF的许可专利权 用于治疗产品的开发。安进公司进行的临床前研究 科学家和同事提供了进一步的证据，KGF具有治疗潜力， 减少暴露于化疗/放疗后对上皮细胞的损伤。一系列临床 临床试验测试了KGF在降低糖尿病的发生率和持续时间方面的安全性和有效性。 在接受强化癌症治疗的患者中发生严重口腔粘膜炎。这项工作最终在 一项成功的3期试验，涉及接受高剂量化疗的恶性血液病患者， 在自体外周血祖细胞移植之前进行大剂量化疗/放疗。 基于这些结果，FDA批准了KGF在该临床背景下的使用， 2005年1月上市（商标名为Kepivance，通用名为Palifermin）。 随后的两项3期临床试验结果表明，帕利弗明是安全的， 对于接受强化化疗并 放射治疗头颈部鳞状细胞癌。