Wu Qing-Li, Buhtoiarov Ilia N, Sondel Paul M, Rakhmilevich Alexander L, Ranheim Erik A
Department of Pathology and Laboratory Medicine, Pediatrics University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
J Immunol. 2009 Jun 1;182(11):6771-8. doi: 10.4049/jimmunol.0801847.
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.
鸸鹋-TCL1转基因小鼠会自发发展出一种类似于人类慢性淋巴细胞白血病（CLL）的CD5(+) B细胞淋巴增殖性疾病。鉴于在这种CLL小鼠模型中T细胞抗肿瘤反应无效，我们试图确定抗CD40单克隆抗体（αCD40）与含CpG的寡脱氧核苷酸（CpG）联合治疗是否能发挥免疫治疗作用。我们之前已经表明，通过CD40和TLR9的顺序连接激活的巨噬细胞在体外和体内都能对实体瘤细胞系产生细胞毒性。在当前研究中，我们发现αCD40加CpG激活的巨噬细胞在体外可诱导肿瘤B细胞凋亡，并且在移植原发性肿瘤B细胞后，αCD40加CpG治疗能显著延缓免疫缺陷SCID/米色小鼠的肿瘤生长。我们的结果提示了一种针对CLL的新型免疫治疗策略，即使面对肿瘤或化疗诱导的T细胞免疫缺陷，该策略可能也是有效的。
