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CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies
Open accessAbstract
Antibody-dependent cell-mediated cytotoxicity (ADCC), which is largely mediated by natural killer (NK) cells, is thought to play an important role in the efficacy of rituximab, an anti-CD20 monoclonal antibody (mAb) used to treat patients with B-cell lymphomas. CD137 is a costimulatory molecule expressed on a variety of immune cells after activation, including NK cells. In the present study, we show that an anti-CD137 agonistic mAb enhances the antilymphoma activity of rituximab by enhancing ADCC. Human NK cells up-regulate CD137 after encountering rituximab-coated tumor B cells, and subsequent stimulation of these NK cells with anti-CD137 mAb enhances rituximab-dependent cytotoxicity against the lymphoma cells. In a syngeneic murine lymphoma model and in a xenotransplanted human lymphoma model, sequential administration of anti-CD20 mAb followed by anti-CD137 mAb had potent antilymphoma activity in vivo. These results support a novel, sequential antibody approach against B-cell malignancies by targeting first the tumor and then the host immune system.
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Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709
Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets
Clynes, R. A., Towers, T. L., Presta, L. G., & Ravetch, J. V. (2000) · Nature Medicine · doi:10.1038/74704 · Cited by 2,768
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Segal, N. H., Logan, T. F., Hodi, F. S., McDermott, D., Melero, I., Hamid, O., Schmidt, H., Robert, C., Chiarion-Sileni, V., Ascierto, P. A., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1272 · Cited by 424
Metadata
- Authors
- Kohrt, H. E., Houot, R., Goldstein, M. J., Weiskopf, K., Alizadeh, A. A., Brody, J., Müller, A., Pachynski, R., Czerwinski, D., Coutre, S., Chao, M. P., Chen, L., Tedder, T. F., & Levy, R.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-02-24
- Volume
- 117
- Issue
- 8
- Pages
- 2423-2432
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2113170011
- Cited by
- 205
- References
- 2
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- bronze
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- Kohrt, H. E., Houot, R., Goldstein, M. J., Weiskopf, K., Alizadeh, A. A., Brody, J., Müller, A., Pachynski, R., Czerwinski, D., Coutre, S., Chao, M. P., Chen, L., Tedder, T. F., & Levy, R. (2011). CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies. Blood. https://doi.org/10.1182/blood-2010-08-301945
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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