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Combination of two anti‐ CD 5 monoclonal antibodies synergistically induces complement‐dependent cytotoxicity of chronic lymphocytic leukaemia cells
Author(s) -
Klitgaard Josephine L.,
Koefoed Klaus,
Geisler Christian,
Gadeberg Ole V.,
Frank David A.,
Petersen Jørgen,
Jurlander Jesper,
Pedersen Mikkel W.
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12503
Subject(s) - antibody dependent cell mediated cytotoxicity , monoclonal antibody , cd52 , cd5 , chronic lymphocytic leukemia , ofatumumab , cytotoxicity , alemtuzumab , cd20 , complement dependent cytotoxicity , epitope , immunology , monoclonal , antibody , cancer research , biology , leukemia , biochemistry , in vitro
Summary The treatment of chronic lymphocytic leukaemia ( CLL ) has been improved by introduction of monoclonal antibodies (m A bs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD 5 and CD 23 along with CD 19 and CD 20, hence anti‐ CD 5 A bs that engage secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of m A bs against human CD 5 was generated and tested for ability to induce complement‐dependent cytotoxicity ( CDC ) and antibody‐dependent cell‐mediated cytotoxicity ( ADCC ) both as single m A bs and combinations of two m A bs against non‐overlapping epitopes on human CD 5. The results demonstrated that combinations of two m A bs significantly increased the level of CDC compared to the single m A bs, while no enhancement of ADCC was seen with anti‐ CD 5 m A b combinations. High levels of CDC and ADCC correlated with low levels of A b‐induced CD 5 internalization and degradation. Importantly, an anti‐ CD 5 m A b combination enhanced CDC of CLL cells when combined with the anti‐ CD 20 m A bs rituximab and ofatumumab as well as with the anti‐ CD 52 m A b alemtuzumab. These results suggest that an anti‐ CD 5 m A b combination inducing CDC and ADCC may be effective alone, in combination with m A bs against other targets or combined with chemotherapy for CLL and other CD 5‐expressing haematological or lymphoid malignancies.