Monoclonal antibody induced growth arrest and cell death in B-cell lymphoma cell lines
Monoclonal antibody induced growth arrest and cell death in B-cell lymphoma cell lines
The therapeutic efficacy of mAb has been shown to vary greatly with respect to both the antibody used and the antigen targeted. This observation has led to the notion that some surface antigens may transduce growth inhibitory signals when ligated. To investigate the role of signalling in therapy and to understand the mechanism by which such therapy is achieved with mAb, the following study was undertaken, using a variety of B-cell lymphoma lines. In particular, the ability of mAb directed to the IgM and CD79 components of BCR were assessed in these cell-lines. mAb targeting the CD20 antigen was similarly assessed.
The data contained in this thesis demonstrate that the IgM region of the BCR is a potent inducer of growth inhibition in some cell-lines, and furthermore, that this effect is due almost entirely to the induction of apoptosis. The extent of cross-linking employed by the anti-IgM mAb was found to be of paramount importance and was correlated in part with the degree of signalling induced by these mAb. Growth inhibition and apoptosis were not induced by antibodies directed to the CD79 region of the BCR, although signalling as measured by changes in intracellular calcium (Ca2+i) and up-regulation of protein tyrosine phosphorylation (PTP), was demonstrated. Potent cross-linking of these mAb did not confer any increase in efficacy.
Certain anti-CD20 mAb produced extremely potent growth inhibition. These effects were shown to be the result of extremely potent activation of the complement system. In high levels of serum (20-30%) the nuclear events undertaken during anti-CD20 death resembled apoptosis, although not all CD20 mAb were similarly efficacious. The DNA fragmentation observed under these conditions appeared to be due to a property of the serum.
The data represented in this thesis help to explain why mAb directed to the BCR and CD20 antigen have been successful in therapy and indicate that at least two possible mechanisms exist for the destruction of tumour by mAb.
University of Southampton
1998
Cragg, Mark Steven
(1998)
Monoclonal antibody induced growth arrest and cell death in B-cell lymphoma cell lines.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The therapeutic efficacy of mAb has been shown to vary greatly with respect to both the antibody used and the antigen targeted. This observation has led to the notion that some surface antigens may transduce growth inhibitory signals when ligated. To investigate the role of signalling in therapy and to understand the mechanism by which such therapy is achieved with mAb, the following study was undertaken, using a variety of B-cell lymphoma lines. In particular, the ability of mAb directed to the IgM and CD79 components of BCR were assessed in these cell-lines. mAb targeting the CD20 antigen was similarly assessed.
The data contained in this thesis demonstrate that the IgM region of the BCR is a potent inducer of growth inhibition in some cell-lines, and furthermore, that this effect is due almost entirely to the induction of apoptosis. The extent of cross-linking employed by the anti-IgM mAb was found to be of paramount importance and was correlated in part with the degree of signalling induced by these mAb. Growth inhibition and apoptosis were not induced by antibodies directed to the CD79 region of the BCR, although signalling as measured by changes in intracellular calcium (Ca2+i) and up-regulation of protein tyrosine phosphorylation (PTP), was demonstrated. Potent cross-linking of these mAb did not confer any increase in efficacy.
Certain anti-CD20 mAb produced extremely potent growth inhibition. These effects were shown to be the result of extremely potent activation of the complement system. In high levels of serum (20-30%) the nuclear events undertaken during anti-CD20 death resembled apoptosis, although not all CD20 mAb were similarly efficacious. The DNA fragmentation observed under these conditions appeared to be due to a property of the serum.
The data represented in this thesis help to explain why mAb directed to the BCR and CD20 antigen have been successful in therapy and indicate that at least two possible mechanisms exist for the destruction of tumour by mAb.
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Published date: 1998
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Local EPrints ID: 463180
URI: http://eprints.soton.ac.uk/id/eprint/463180
PURE UUID: c847df8c-fbc9-4941-a229-aff5b71dedca
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Date deposited: 04 Jul 2022 20:47
Last modified: 04 Jul 2022 20:47
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Author:
Mark Steven Cragg
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