Abstract |
Bispecific monoclonal antibodies (bi-mAb), directed against a tumor-associated antigen and the CD3 or CD28 antigen on T lymphocytes, induce activation of resting T lymphocytes and target-specific tumor cell lysis. We now show that both necrosis and apoptosis contribute to T-cell-mediated tumor cell destruction. Even though T cells up-regulate FAS/APO-1 expression upon bi-mAb stimulation, FAS/APO-1-mediated apoptosis does not contribute to bi-mAb-mediated destruction of Hodgkin's cells. CD8+ lymphocytes were the most potent effectors of bi-mAb-mediated cytotoxicity and had the highest levels of mRNA coding for perforin and granzyme A and B. Ca2+-complexing agents, which abrogate perforin activity, led to decreased levels of necrosis, while inhibition of granzyme activity in effector or target cells had a similar effect on apoptosis. Granzyme-mediated apoptosis critically dependent on the proliferative state of the target cells, while perforin-induced necrosis was not cell-cycle-dependent. Our results underline the importance of the expression levels of perforin and granzymes in the effector T cells and of the proliferative state of the target cells in bi-mAb-mediated apoptosis and necrosis of tumor cells.
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Authors | C Renner, G Held, S Ohnesorge, S Bauer, K Gerlach, J P Pfitzenmeier, M Pfreundschuh |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 44
Issue 2
Pg. 70-6
(Apr 1997)
ISSN: 0340-7004 [Print] Germany |
PMID | 9177467
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Bispecific
- Antigens, CD
- Membrane Glycoproteins
- Pore Forming Cytotoxic Proteins
- fas Receptor
- Perforin
- GZMB protein, human
- Granzymes
- Serine Endopeptidases
- GZMA protein, human
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Topics |
- Antibodies, Bispecific
(immunology)
- Antibody-Dependent Cell Cytotoxicity
(immunology)
- Antigens, CD
(immunology)
- Apoptosis
- Blotting, Northern
- Cytotoxicity, Immunologic
(immunology)
- DNA Fragmentation
- Granzymes
- Hodgkin Disease
(pathology)
- Humans
- Lymphocyte Activation
(physiology)
- Membrane Glycoproteins
(physiology)
- Necrosis
- Perforin
- Pore Forming Cytotoxic Proteins
- Serine Endopeptidases
(physiology)
- T-Lymphocytes, Cytotoxic
(immunology)
- fas Receptor
(physiology)
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