Journal article
Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model
Blood, Vol.114(26), pp.5322-5330
Lymphoid Neoplasia
12/17/2009
DOI: 10.1182/blood-2009-01-200469
PMCID: PMC2796137
PMID: 19805620
Abstract
Growing evidence indicates antibody-dependent cellular cytotoxicity (ADCC) contributes to the clinical response to monoclonal antibody (mAb) therapy of lymphoma. Recent in vitro analysis suggests C3b can inhibit mAb-induced natural killer (NK)–cell activation and ADCC. Further studies were conducted to assess the effect of C3 depletion on mAb-induced NK activation and therapy of lymphoma. Normal human serum inhibited the ability of rituximab-coated lymphoma cells to activate NK cells as previously reported. Serum did not inhibit NK-cell activation when it was preincubated with cobra venom factor (CVF) to deplete C3. Similar results were found when transudative pleural fluid or nonmalignant ascites was used as surrogates for extravascular fluid, suggesting the inhibitory effect of complement may be present in the extravascular compartment, in which many malignant lymphocytes reside. In vivo, C3 was depleted before mAb treatment in a syngeneic murine model of lymphoma. Survival of lymphoma-bearing mice after treatment with CVF plus mAb and with a human C3 derivative with CVF-like functions (HC3-1496) plus mAb was both superior to that of mAb alone. These studies show that complement depletion enhances NK-cell activation induced by rituximab-coated target cells and improves the efficacy of mAb therapy in a murine lymphoma model.
Details
- Title: Subtitle
- Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model
- Creators
- Siao-Yi Wang - University of Iowa, Iowa CitySuresh Veeramani - University of Iowa, Iowa CityEmilian Racila - University of Iowa, Iowa CityJeffrey Cagley - University of Iowa, Iowa CityDavid C Fritzinger - Cancer Research Center of Hawaii, Honolulu; andCarl-Wilhelm Vogel - Cancer Research Center of Hawaii, Honolulu; andWilliam St John - InCode Biopharmaceutics Inc, San Diego, CAGeorge J Weiner - University of Iowa, Iowa City
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.114(26), pp.5322-5330
- Publisher
- American Society of Hematology
- Series
- Lymphoid Neoplasia
- DOI
- 10.1182/blood-2009-01-200469
- PMID
- 19805620
- PMCID
- PMC2796137
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Grant note
- P50 CA97274 / National Institutes of Health
- Language
- English
- Date published
- 12/17/2009
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984094378202771
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