title: Interleukin-15 enhances rituximab-dependent cytotoxicity against chronic lymphocytic leukemia cells and overcomes transforming growth factor beta-mediated immunosuppression.
abstract: Chemoimmunotherapy with anti-CD20 monoclonal antibody rituximab is increasingly used for the treatment of patients with chronic lymphocytic leukemia (CLL). Antibody-dependent cytotoxicity (ADCC) is one of the most important mechanisms of action of rituximab against B-cell malignancies. We studied ways to increase the cytotoxic effect of rituximab on CLL cells by enhancing ADCC. Peripheral blood mononuclear cell (PBMC) or purified natural killer (NK) cells from healthy donors were activated with interleukin-15 (IL-15) and cultured with rituximab-coated CLL cells, and ADCC was evaluated using a (51)chromium release assay. The IL-15 significantly enhanced in vitro ADCC against CLL cells, and this effect was mainly mediated by NK cells. The IL-15 treated effector cells with the low affinity FcγRIIIA receptor (158FF) had an ADCC comparable to those with the high affinity FcγRIIIA form (158VF). In addition, IL-15 enhanced rituximab-mediated ADCC of CLL cells in the presence of transforming growth factor-beta. The IL-15 increases rituximab-mediated ADCC against CLL, and supports the use of such agents with the goal of improving clinical response to chemoimmunotherapy in patients with CLL.
authors.affiliation: Department of Immunology, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Moga
authors.forename: Elisabet
authors.initials: E
authors.lastname: Cantó
authors.forename: Silvia
authors.initials: S
authors.lastname: Vidal
authors.forename: Cándido
authors.initials: C
authors.lastname: Juarez
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D000970:Antineoplastic Agents; D003603:Cytotoxins; D004336:Drug Antagonism; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D019409:Interleukin-15 / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000473:pathology*; D000069283:Rituximab; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D003603:Cytotoxins; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D016212:Transforming Growth Factor beta; D000069283:Rituximab