Lefebvre, Marie-Laure and Krause, Stfan W. and Salcedo, Margarita and Nardin, Alessandra (2006) Ex vivo-activated human macrophages kill chronic lymphocytic leukemia cells in the presence of rituximab: Mechanism of anti body-dependent cellular cytotoxicity and impact of human serum. JOURNAL OF IMMUNOTHERAPY, 29 (4). pp. 388-397. ISSN 1524-9557,
Full text not available from this repository. (Request a copy)Abstract
Anti body-dependent cellular cytotoxicity (ADCC) is one of the mechanisms of tumor killing during antibody (Ab) immunotherapy, and a role for myeloid cells as effectors has been observed in several models. We are developing immunotherapy approaches based on administration of large numbers of ex vivo interferon-gamma-activated macrophages to cancer patients. With a quantitative assay measuring killing of nonproliferating tumor cells, we evaluated whether, in physiologic conditions, these macrophages synergize with the anti-CD20 Ab rituximab for killing primary B-cell chronic lymphocytic leukemia (B-CLL) cells. ADCC reached levels of 70% to 80% at effector to target ratios as low as 1:1. Macrophage recruitment by Ab-opsonized tumor cells did not result in enhanced cytokine secretion, suggesting that the cytokine shower observed in rituximab-treated patients is not caused by macrophage activation, and that cytokines have no role in CLL killing. We observed that uptake of tumor material by macrophages was not directly correlated to tumor killing. Nonetheless, experiments in the presence of cytochalasin D showed that ADCC occurred mainly by phagocytosis. Tumor killing was largely mediated by Fc gamma RI and inhibited by increasing concentration of serum. Importantly, complement deposition on B-CLL cells did not seem to enhance macrophage ADCC in this model, as complement-depleted and complement-repleted human plasmas exerted comparable inhibition.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NON-HODGKINS-LYMPHOMA; ANTI-CD20 MONOCLONAL-ANTIBODY; COLONY-STIMULATING FACTOR; FC-GAMMA-RIIIA; HUMAN-MONOCYTES; B-CELLS; ADOPTIVE IMMUNOTHERAPY; FUNCTIONAL-PROPERTIES; THERAPEUTIC ACTIVITY; TUMOR-CELLS; macrophages; CD20; rituximab; chronic lymphocytic leukemia; antibody-dependent cellular cytotoxicity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Feb 2021 09:36 |
| Last Modified: | 11 Feb 2021 09:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34375 |
Actions (login required)
 |
View Item |
