Tumoricidal Effects of Activated Macrophages in a Mouse Model of Chronic Lymphocytic Leukemia

The E mu-TCL1 transgenic mouse spontaneously develops a CD5(+) B cell lymphoproliferative disorder similar to human chronic lymphocytic leukemia (CLL). Given the ineffectual T cell antitumor responses in this mouse model of CLL, we sought to determine whether combined treatment with anti-CD40 mAb (alpha CD40) and CpG-containing oligodeoxynucleotides (CpG) could exert immunotherapeutic effects. We have previously shown that macrophages activated by sequential ligation of CD40 and TLR9 could become cytotoxic against solid tumor cell lines both in vitro and in vivo. In the current study, we find that alpha CD40 plus CpG-activated macrophages induce tumor B cell apoptosis in vitro and that alpha CD40 plus CpG treatment markedly retards tumor growth in immunodeficient SCID/Beige mice following transplantation of primary tumor B cells. Our results suggest a novel immunotherapeutic strategy for CIA, that may be effective even in the face of tumor or chemotherapy-induced T cell immunodeficiency. The Journal of Immunology, 2009, 182: 6771-6778.