Tumoricidal effects of activated macrophages in a mouse model of chronic lymphocytic leukemia.
The Emu-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 (alphaCD40) 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 alphaCD40 plus CpG-activated macrophages induce tumor B cell apoptosis in vitro and that alphaCD40 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 CLL that may be effective even in the face of tumor or chemotherapy-induced T cell immunodeficiency.
Wu
Qing-Li
QL
Department of Pathology and Laboratory Medicine, Pediatrics University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Buhtoiarov
Ilia N
IN
Sondel
Paul M
PM
Rakhmilevich
Alexander L
AL
Ranheim
Erik A
EA
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology; D019013:CD40 Antigens / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008262:Macrophage Activation; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology
D019013:CD40 Antigens; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides