《科学--转化医学》24日刊登的一篇研究报告称，系统性红斑狼疮抗体会使癌细胞对化疗变得更为敏感。系统性红斑狼疮是一种自身免疫系统疾病，它会攻击身体自身的健康细胞和组织。这些发现是人们第一次证明狼疮抗体可潜在地用于治疗癌症。
系统性红斑狼疮是一种影响全世界5百多万人的自身免疫性疾病。这项研究可帮助解释在罹患狼疮的患者中有着意想不到的乳腺癌、卵巢癌和前列腺癌的低发病率。
这是耶鲁大学医学院、耶鲁大学癌症中心及加州大学等研究机构共同参与的一项研究。James Hansen及其同事在实验室中确认了一种叫做3E10的狼疮抗体可使卵巢肿瘤对放疗敏感。狼疮抗体是通过穿透细胞并附着于DNA从而打乱了修复DNA所需的细胞机器而发挥作用的。在没有修复DNA的能力时，细胞对像放疗等损伤DNA的疗法会变得更为敏感。
令人意外的是，该抗体本身（无需放疗或化疗）可杀灭DNA修复有缺陷的像乳腺癌、卵巢癌或前列腺癌等的癌细胞。
这些结果提示，该抗体可用来作为一种攻击DNA修复有缺陷的癌细胞的新疗法，但同时又不会伤害正常细胞。另外，用于本研究的这种抗体已经作为一种狼疮疫苗，在人体的临床试验中通过了测试并被认为是安全的。
Targeting Cancer with a Lupus Autoantibody.
James E. Hansen, Grace Chan, Yanfeng Liu, Denise C. Hegan, Shibani Dalal1, Eloise Dray, Youngho Kwon, Yuanyuan Xu, Xiaohua Xu, Elizabeth Peterson-Roth, Erik Geiger, Yilun Liu, Joseph Gera, Joann B. Sweasy, Patrick Sung, Sara Rockwell, Robert N. Nishimura, Richard H. Weisbart and Peter M. Glazer
Abstract：Systemic lupus erythematosus (SLE) is distinct among autoimmune diseases because of its association with circulating autoantibodies reactive against host DNA. The precise role that anti-DNA antibodies play in SLE pathophysiology remains to be elucidated, and potential applications of lupus autoantibodies in cancer therapy have not previously been explored. We report the unexpected finding that a cell-penetrating lupus autoantibody, 3E10, has potential as a targeted therapy for DNA repair–deficient malignancies. We find that 3E10 preferentially binds DNA single-strand tails, inhibits key steps in DNA single-strand and double-strand break repair, and sensitizes cultured tumor cells and human tumor xenografts to DNA-damaging therapy, including doxorubicin and radiation. Moreover, we demonstrate that 3E10 alone is synthetically lethal to BRCA2-deficient human cancer cells and selectively sensitizes such cells to low-dose doxorubicin.
