Sadeghi Solmaz, Kalhor Hourieh, Panahi Mohammad, Abolhasani Hoda, Rahimi Bahareh, Kalhor Reyhaneh, Mehrabi Amirmehdi, Vahdatinia Mahsa, Rahimi Hamzeh
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
Int J Biol Macromol. 2021 Nov 30;191:1175-1190. doi: 10.1016/j.ijbiomac.2021.09.151. Epub 2021 Oct 1.
Palifermin (Kepivance™) is the first therapeutic approved by the Food and Drug Administration for preventing and managing the oral mucositis provoked by myelotoxic and mucotoxic therapies. Palifermin is a recombinant protein generated from human keratinocyte growth factor (KGF) and imitates the function of endogenous KGF. KGF is an epithelial mitogen involved in various biological processes which belongs to the FGF family. KGF possesses a high level of receptor specificity and plays an important role in tissue repair and maintaining of the mucosal barrier integrity. Based on these unique features, palifermin was developed to enhance the growth of damaged epithelial tissues. Administration of palifermin has shown success in the reduction of toxicities of chemotherapy and radiotherapy, and improvement of the patient's quality of life. Notwithstanding all merits, the clinical application of palifermin is limited owing to its instability and production challenges. Hence, a growing number of ongoing researches are designed to deal with these problems and enhance the physicochemical and pharmaceutical properties of palifermin. In the current review, we discuss KGF structure and function, potential therapeutic applications of palifermin, as well as the latest progress in the production of recombinant human KGF and its challenges ahead.
帕利夫明(凯普仙™)是美国食品药品监督管理局批准的首个用于预防和管理由骨髓毒性和黏膜毒性疗法引发的口腔黏膜炎的治疗药物。帕利夫明是一种由人角质形成细胞生长因子(KGF)生成的重组蛋白,模拟内源性KGF的功能。KGF是一种参与多种生物学过程的上皮细胞有丝分裂原,属于成纤维细胞生长因子(FGF)家族。KGF具有高度的受体特异性,在组织修复和维持黏膜屏障完整性方面发挥着重要作用。基于这些独特特性,开发了帕利夫明以促进受损上皮组织的生长。帕利夫明的给药已成功降低了化疗和放疗的毒性,并改善了患者的生活质量。尽管有诸多优点,但由于其不稳定性和生产挑战,帕利夫明的临床应用受到限制。因此,越来越多正在进行的研究旨在解决这些问题并增强帕利夫明的物理化学和药学性质。在本综述中,我们讨论了KGF的结构和功能、帕利夫明的潜在治疗应用,以及重组人KGF生产的最新进展及其面临的挑战。