Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA.
Cancer Res. 2012 Nov 1;72(21):5556-65. doi: 10.1158/0008-5472.CAN-12-0173. Epub 2012 Sep 17.
Most patients with lung cancer still die from their disease, necessitating additional options to improve treatment. Here, we provide evidence for targeting CD22, a cell adhesion protein known to influence B-cell survival that we found is also widely expressed in lung cancer cells. In characterizing the antitumor activity of an established anti-CD22 monoclonal antibody (mAb), HB22.7, we showed CD22 expression by multiple approaches in various lung cancer subtypes, including 7 of 8 cell lines and a panel of primary patient specimens. HB22.7 displayed in vitro and in vivo cytotoxicity against CD22-positive human lung cancer cells and tumor xenografts. In a model of metastatic lung cancer, HB22.7 inhibited the development of pulmonary metastasis and extended overall survival. The finding that CD22 is expressed on lung cancer cells is significant in revealing a heretofore unknown mechanism of tumorigenesis and metastasis. Our work suggests that anti-CD22 mAbs may be useful for targeted therapy of lung cancer, a malignancy that has few tumor-specific targets.
大多数肺癌患者仍死于该疾病,因此需要额外的治疗选择来改善治疗效果。在这里,我们提供了针对 CD22 的证据,CD22 是一种已知会影响 B 细胞存活的细胞黏附蛋白,我们发现它也在肺癌细胞中广泛表达。在对一种已建立的抗 CD22 单克隆抗体 (mAb) HB22.7 的抗肿瘤活性进行表征时,我们通过多种方法在多种肺癌亚型中发现了 CD22 的表达,包括 8 个细胞系中的 7 个和一组原发性患者标本。HB22.7 在体外和体内对 CD22 阳性的人肺癌细胞和肿瘤异种移植物显示出细胞毒性。在转移性肺癌模型中,HB22.7 抑制了肺转移的发展并延长了总生存期。CD22 在肺癌细胞上的表达表明了肿瘤发生和转移的一个未知机制,这一发现具有重要意义。我们的工作表明,抗 CD22 mAbs 可能对肺癌的靶向治疗有用,因为肺癌很少有肿瘤特异性靶点。