Abstract |
Bispecific monoclonal antibodies (Bi-mAbs) specific for a tumor-associated antigen and the CD3 or CD28 antigen on T lymphocytes represent one of the most successful experimental strategies for the immunotherapy of cancer. We report that the in vivo administration of both alpha-CD3/CD30 and alpha-CD28/CD30 Bi-mAbs results in the specific activation of xenotransplanted, resting human T cells infiltrating the CD30-positive Hodgkin's tumor. Bi-mAb treatment resulted in enhanced expression of cytokines such as interleukin 1beta, interleukin 2, tumor necrosis factor type alpha, and activation markers including Ki-67, CD25, and CD45RO in tumor-infiltrating lymphocytes. This antigen-dependent, local T-cell stimulation led to the activation of the cytolytic machinery in T lymphocytes, determined by the up-regulation of mRNA-encoding perforin and the cytotoxic serine- esterases granzymes A and B. The Bi-mAb-induced generation of CTLs depended on the presence of the CD30 antigen and the combined application of both Bi-mAbs. Our findings suggest that the combined application of T-cell-activating Bi-mAbs is able to achieve a tumor site-specific activation of the T-cell cytolytic machinery in vivo. The fact that these cytotoxic cells do not home in tumor-associated antigen-negative tissue and do not enter circulation might explain our previous observations (C. Renner et al., Blood, 87: 2930-2937, 1996) of a high cure rate in preclinical models even at an advanced stage of disease.
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Authors | S Bauer, C Renner, J P Juwana, G Held, S Ohnesorge, K Gerlach, M Pfreundschuh |
Journal | Cancer research
(Cancer Res)
Vol. 59
Issue 8
Pg. 1961-5
(Apr 15 1999)
ISSN: 0008-5472 [Print] United States |
PMID | 10213507
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Bispecific
- Cytokines
- Membrane Glycoproteins
- Pore Forming Cytotoxic Proteins
- Tumor Necrosis Factor Receptor Superfamily, Member 7
- Perforin
- Serine Endopeptidases
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Topics |
- Animals
- Antibodies, Bispecific
(therapeutic use)
- Cytokines
(metabolism)
- Humans
- Immunotherapy
- Lymphocyte Activation
- Membrane Glycoproteins
(metabolism)
- Mice
- Mice, SCID
- Neoplasm Transplantation
- Neoplasms, Experimental
(immunology, therapy)
- Perforin
- Pore Forming Cytotoxic Proteins
- Serine Endopeptidases
(metabolism)
- Tumor Cells, Cultured
- Tumor Necrosis Factor Receptor Superfamily, Member 7
(biosynthesis)
- Up-Regulation
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