Comparison of the in vitro effects of the anti‐CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells

• Published in: British journal of haematology 2011-02, Vol.152 (3), p.295-306
• Main Authors: Patz, Michaela, Isaeva, Polina, Forcob, Nche, Müller, Bianka, Frenzel, Lukas P., Wendtner, Clemens‐Martin, Klein, Christian, Umana, Pablo, Hallek, Michael, Krause, Günter
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antibodies; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived - pharmacology; Antibody-Dependent Cell Cytotoxicity - drug effects; Antigens, CD20 - immunology; Antigens, CD20 - metabolism; Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; B cell depletion; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Biological and medical sciences; CD20; CD20 antigen; Cell death; Chemotherapy; Chlorambucil; Chronic lymphatic leukemia; chronic lymphocytic leukaemia; Cytotoxicity; direct cell death; Drug Screening Assays, Antitumor; Female; Hematologic and hematopoietic diseases; Humans; immunotherapy; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Depletion - methods; Lymphocytes B; Lymphocytes T; Male; Medical sciences; Middle Aged; Oligonucleotides; phosphatidylserine; Rituximab; Tumor Cells, Cultured
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2010.08428.x

Summary The effects of two CD20 antibodies, namely rituximab, the current standard for treatment of chronic lymphocytic leukaemia (CLL) in combination with chemotherapy, and GA101, a glyco‐engineered type II antibody were compared on CLL cells ex vivo. Antibody‐induced phosphatidylserine exposure was examined in isolated CLL cells. For a more comprehensive assessment of antibody‐mediated cell killing including Fc‐mediated mechanisms, B cell depletion from whole blood samples was monitored. Treatment with rituximab or GA101 reduced the average viability of isolated CLL cells by 6% or 11%, and the ratio of B to T cells in whole blood samples by 12% or 33%, respectively. Combination with GA101 enhanced the cytotoxicity of the chemotherapeutic agent chlorambucil on isolated CLL cells. CD20 surface expression on CLL cells correlated with GA101‐induced B cell depletion, but not with direct cell death induction. Treatment of whole blood samples from CLL patients with a CpG‐containing oligonucleotide increased CD20 expression on CLL cells and GA101‐dependent B cell depletion. Despite the variable responses of individual CLL samples, the CLL cell depletion from whole blood by GA101 was consistently much stronger than by rituximab, which argues for clinical investigation of GA101 in CLL patients.