Item type:Thesis, Open Access

Entwicklung eines Antikörper- Assays zur Risikoabschätzung anaphylaktischer Reaktionen sowie der Inaktivierungswahrscheinlichkeit des Enzyms L- Asparaginase in der Therapie der akuten lymphatischen Leukämie

Thumbnail Image

Files

djvr.pdf (1.09 MB)

Date

2005-06-09

Authors

Publisher

Philipps-Universität Marburg
DOI

Supervisors

Abstract

L-asparaginase is a bacterial enzyme that has been used for over thirty years for polychemotherapy of acute lymphatic leukaemia and some malignant lymphomas. Asparaginase catalyzes the hydrolysis of L-asparaginase, which leads to depletion of asparagine in blood plasma. Since this amino acid is essential for tumor growth, the low concentration of asparagine consequently suppresses the replication of malignant cells. Major complications during therapy with asparaginase are hypersensitivity reactions and a so-called silent inactivation of the enzyme. Prediction of a potential hypersensitivity reaction or a silent inactivation would lead to a significant improvement in therapy with asparaginase. The immunological test that has been used to detect serum antibodies that might be responsible for hypersensitivity reactions or silent inactivation shows poor sensitivity and specificity. This test is therefore not helpful for predicting complications of aspariginase therapy. Based on the hypothesis that the antibodies are epitope specific, asparaginase-DNA was digested without knowledge of the precise location of the epitopes to obtain five asparaginase fragments with a known amino acid sequence. The use of these fragments as antigens allowed identification of an early antibody population against the c-terminal fragment (237-326) in patients with silent inactivation. A correlation between antibody titer against one of the other fragments and silent inactivation could not be found. These results establish a promising basis for further development of this assay. By performing distinct epitope mapping, the fragments used for immunological tests will be more selective in the future. Further tests in patients receiving aspariginase therapy will be necessary to statistically verify the predictive value of this new approach.

Review

Metadata

Contributors
Supervisor:
Dates
Created: 2005Issued: 2005-06-09Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2005.0264
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Anaphylactic reactionAsparaginaseSilent inactivationAcute lymphatic leukaemiaStille InaktivierungAnaphylaktische Reaktion
DFG-subjects
AsparaginaseAkute lymphatische Leukämie
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2005.0264
show more
Randow, Josefine von (130015652): Entwicklung eines Antikörper- Assays zur Risikoabschätzung anaphylaktischer Reaktionen sowie der Inaktivierungswahrscheinlichkeit des Enzyms L- Asparaginase in der Therapie der akuten lymphatischen Leukämie. : Philipps-Universität Marburg 2005-06-09. DOI: https://doi.org/10.17192/z2005.0264.

License

item.page.license.under-copyright
This item has been published with the following license: In Copyright