In vitro testing of monoclonal antibody rituximab on cells of B-cell chronic lymphocytic leukemia

Název česky In vitro testování monoklonální protilátky rituximab na buňkách B-CLL


Rok publikování 2007
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Lékařská fakulta

Popis B cell chronic lymphocytic leukemia (B CLL) is the most common adult leukemia in the Western world. The disease is generally treated by purine analogs or alkylator agents. Utility of monoclonal antibodies (Mab), e.g. rituximab: antiCD20 or alemtuzumab antiCD52, represents a modern trend in a nowadays oncology. The efficacy of the B cell specific Mab rituximab is, however, limited when used as a monotherapy. Promising results are being obtained, on the contrary, when the rituximab is combined with some standard chemotherapeutics. We tested this possibility for the most frequently used drug fludarabine, on our cohort of B CLL samples characterized for two key tumor suppressors, the p53 and ATM. A cell viability assay (WST1) was used for the detection. The rituximab itself applied in a standard concentration (10ug/ml) manifested a diverse effect on the B CLL cells, with increasing a metabolic activity of some but decreasing in other samples. This phenomenon, which we study now in more details, was independent on the status of the monitored genes. Resistance to fludarabin was obviously high in the samples bearing the p53 inactivation but not in the ones harboring the ATM deletion. The latter samples were even more senzitive to fludarabine than the wild type cells. Sensitization by a standard dose of rituximab (applied for 72h) to subsequently used fludarabin (48h) in four different concentrations was possible for some samples of all the three categories. The p53/ATM status is thus important for the sensitivity to fludarabin itself, but does not count for the potentiation effect of rituximab. Recently, we are trying to elucidate the mechanism behind rituximab action by using modern genomic (DNA microarray) and proteomic (2D elfo and MS detection) approaches.

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