Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Investigation of monoclonal antibodies generated against the growth hormone receptor on growth hormone signaling ; Untersuchung von monoklonalen Antikörpern gegen den Somatotropin-Rezeptor auf die Somatropin Signalgebung
The development of monoclonal antibodies (mAbs) targeting the GHR aimed at lowering the expression of IGF-1 was the main focus of this dissertation. The significance of the project is based on the fact that IGF-1 is associated with a variety of age-related diseases. Hence, the development and characterization of mAbs targeting the GH-IGF-1 axis with the potential to downregulate IGF-1 expression could result in the prevention of such age-related diseases and the augmentation of therapeutic outcomes of age-related diseases. The initial part of the project constituted the production of five selected hybridoma clones, which produce five individual α-GHR mAbs targeting different structures of the GHR. Three out of five clones were successfully produced and were the subject of further testing: α-GHR562, α-GHR565, and α-GHR592. In vitro experiments aimed at assessing binding specificity and affinity, the ability to downregulate STAT5 and ERK1/2 phosphorylation, as well as IGF-1 luciferase promoter reporter activity, showed variable characteristics of the tested mAbs. Binding affinity for candidates α-GHR562 and α-GHR592 could be determined, but no binding of α-GHR565 could be detected. Furthermore, all three mAbs significantly downregulated STAT5 phosphorylation, a marker tested for any immediate effects of mAbs on GH signaling. However, none of the tested mAbs induced any significant changes in the phosphorylation of ERK1/2 and the IGF-1 luciferase promoter reporter activity tests. Testing of the mAbs in vivo revealed no significant effect of α-GHR562 or α-GHR565 on circulating IGF-1 levels. On the other hand, significant increases in serum ALT (alanine transaminase) levels was observed after α-GHR592 treatment, indicative of induced liver toxicity. Additionally, an increase in the general immune response marker SAP (serum amyloid protein) was detected, however this increase was not significant. Interpretation of the compiled data set might indicate that, out of the tested mAbs, α-GHR592 might be the most promising ...
Investigation of monoclonal antibodies generated against the growth hormone receptor on growth hormone signaling ; Untersuchung von monoklonalen Antikörpern gegen den Somatotropin-Rezeptor auf die Somatropin Signalgebung
The development of monoclonal antibodies (mAbs) targeting the GHR aimed at lowering the expression of IGF-1 was the main focus of this dissertation. The significance of the project is based on the fact that IGF-1 is associated with a variety of age-related diseases. Hence, the development and characterization of mAbs targeting the GH-IGF-1 axis with the potential to downregulate IGF-1 expression could result in the prevention of such age-related diseases and the augmentation of therapeutic outcomes of age-related diseases. The initial part of the project constituted the production of five selected hybridoma clones, which produce five individual α-GHR mAbs targeting different structures of the GHR. Three out of five clones were successfully produced and were the subject of further testing: α-GHR562, α-GHR565, and α-GHR592. In vitro experiments aimed at assessing binding specificity and affinity, the ability to downregulate STAT5 and ERK1/2 phosphorylation, as well as IGF-1 luciferase promoter reporter activity, showed variable characteristics of the tested mAbs. Binding affinity for candidates α-GHR562 and α-GHR592 could be determined, but no binding of α-GHR565 could be detected. Furthermore, all three mAbs significantly downregulated STAT5 phosphorylation, a marker tested for any immediate effects of mAbs on GH signaling. However, none of the tested mAbs induced any significant changes in the phosphorylation of ERK1/2 and the IGF-1 luciferase promoter reporter activity tests. Testing of the mAbs in vivo revealed no significant effect of α-GHR562 or α-GHR565 on circulating IGF-1 levels. On the other hand, significant increases in serum ALT (alanine transaminase) levels was observed after α-GHR592 treatment, indicative of induced liver toxicity. Additionally, an increase in the general immune response marker SAP (serum amyloid protein) was detected, however this increase was not significant. Interpretation of the compiled data set might indicate that, out of the tested mAbs, α-GHR592 might be the most promising ...
Investigation of monoclonal antibodies generated against the growth hormone receptor on growth hormone signaling ; Untersuchung von monoklonalen Antikörpern gegen den Somatotropin-Rezeptor auf die Somatropin Signalgebung
Gün, Esra (Autor:in) / Knauer, Shirley
04.07.2022
Hochschulschrift
Elektronische Ressource
Englisch
GROWTH HORMONE AND MAMMARY GROWTH
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