Department of Healthcare Surveillance and Bioethics, Section of Pharmacology, Catholic University Medical School, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
Growth Factors. 2022 Jun;40(1-2):37-45. doi: 10.1080/08977194.2022.2060095. Epub 2022 Apr 20.
CHF6467 is a mutated form of human recombinant nerve growth factor (NGF). The mutation selectively disrupts the binding of NGF to its p75NTR receptor while maintaining the affinity toward TrkA receptor. Because of such different profile of receptor interaction, CHF6467 maintains unaltered the neurotrophic and neuroprotective properties of wild-type NGF but shows reduced algogenic activity.In this study, we investigated the effects of CHF6467 on mortality, proliferation, cell-damage and migration in three human glioblastoma cell lines (U87MG, T98G, LN18), and in the rat astrocytoma C6 cells. Both CHF6467 and wild-type NGF, given in the range 1-50 ng/ml, did not modify cell proliferation, metabolism and migration, as well as the number of live/dead cells.The present data are predictive of a lack of tumorigenic activity by both wild-type NGF and CHF6467 on these cell types , and warrant for CHF6467 further clinical development.
CHF6467 是一种人重组神经生长因子（NGF）的突变形式。该突变选择性地破坏了 NGF 与其 p75NTR 受体的结合，同时保持了对 TrkA 受体的亲和力。由于这种受体相互作用的不同特征，CHF6467 保持了野生型 NGF 的神经营养和神经保护特性不变，但降低了致痛活性。在这项研究中，我们研究了 CHF6467 对三种人神经胶质瘤细胞系（U87MG、T98G、LN18）和大鼠星形细胞瘤 C6 细胞的死亡率、增殖、细胞损伤和迁移的影响。CHF6467 和野生型 NGF 在 1-50ng/ml 的范围内均未改变细胞增殖、代谢和迁移，以及活/死细胞的数量。这些数据预测野生型 NGF 和 CHF6467 对这些细胞类型均无致瘤活性，并为 CHF6467 的进一步临床开发提供了依据。
