In:
Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 29, No. 42 ( 2022-12), p. 6463-6478
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0929-8673
DOI:
10.2174/0929867328666211117093401
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
SSG:
15,3
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