In Vitro Sensitivity Testing in the Assessment of Anti-CLL Drug Candidates

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of morphologically mature, but immuno-incompetent B-lymphocytes in the bone marrow, peripheral blood, spleen and lymphoid organs. With an annual incidence of about 2-3/ 100000 in the general population (Hamblin, 2009), CLL represents a frequent leukemia type. Since CLL mostly affects persons of advanced age, the incidence among persons above 65 years reaches ten times this frequency (Eichhorst et al., 2009). Moreover CLL follows a remarkably heterogeneous course, emphasizing the need for personalized treatment approaches. Despite recent advances in CLL therapy, the disease still remains incurable and new treatment options need to be developed (Hallek et al., 2008). New insights into CLL biology have started to result in new targeted, sometimes patient group-specific treatment approaches (Pleyer et al., 2009; Zenz et al., 2010). Candidate substances for pre-clincial assays are mostly molecularly targeted drugs, i.e. either small molecules interfering with intracellular signaling (Wickremasinghe et al., 2011) or mononoclonal antibodies (Jaglowski et al., 2010). As examples we will discuss in this chapter the pre-clinical assessment of protein and lipid kinase inhibitors and of monoclonal antibodies.