前胸腺素及其C端免疫反应性十肽无急性毒性证据：计算机模拟、体外和体内研究初探

Title:Prothymosin α and its C-Terminal Immunoreactive Decapeptide Show No Evidence of Acute Toxicity: A Preliminary In Silico, In Vitro and In Vivo Investigation

Volume: 29 Issue: 42

关键词: 潮湿，前胸腺素α，体内毒性，免疫调节，胸腺肽，胸腺素α1。

摘要:

Background: Members of the α-thymosin family have long been studied for their immunostimulating properties. Among them, the danger-associated molecular patterns (DAMPs) prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) have been shown to act as immunomodulators in vitro, due to their ability to promote T helper type 1 (Th1) responses. Recently, we verified these findings in vivo, showing that both proTα and proTα(100-109) enhance antitumor-reactive T cell-mediated responses.

Methods: In view of the eventual use of proTα and proTα(100-109) in humans, we investigated their safety profile in silico, in human leukocytes and cancer cell lines in vitro, and in immunocompetent mice in vivo, in comparison to the proTα derivative thymosin alpha 1 (Τα1), a 28-mer peptide extensively studied for its safety in clinical trials.

Results: In silico prediction via computational tools showed that all three peptide sequences likely are non-toxic or do not induce allergic regions. In vitro, pro- Tα, proTα(100-109) and Tα1 did not affect the viability of human cancer cell lines and healthy donor-derived leukocytes, did not promote apoptosis or alter cell cycle distribution. Furthermore, mice injected with proTα, proTα(100-109) and Tα1 at doses equivalent to the suggested dose regimen of Tα1 in humans, did not show signs of acute toxicity, whereas proTα and proTα(100-109) increased the levels of proinflammatory and Th1- type cytokines in their peripheral blood.

Conclusion: Our preliminary findings suggest that proTα and proTα(100-109), even at high concentrations, are non-toxic in vitro and in an acute toxicity model in vivo; moreover, we show that the two peptides retain their immunomodulatory properties in vivo and, eventually, could be considered for therapeutic use in humans.

Cite this article as:

Prothymosin α and its C-Terminal Immunoreactive Decapeptide Show No Evidence of Acute Toxicity: A Preliminary In Silico, In Vitro and In Vivo Investigation, Current Medicinal Chemistry 2022; 29 (42) . https://dx.doi.org/10.2174/0929867328666211117093401