Kim Sae Won, Park Han Wook, Kim Hyekang, Lee Seungwon, Choi So Young, Park Yunji, Lee Seung-Woo
Research Institute, SL-BIGEN Inc., Seongnam 13488, Korea.
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37673, Korea.
Immune Netw. 2019 Nov 19;19(6):e43. doi: 10.4110/in.2019.19.e43. eCollection 2019 Dec.
A full-length translational product of the gene, KIAA1114, is a distinctive marker of cancer stem cells in human hepatocellular carcinoma, and a mAb, Kiatomab, is specific to KIAA1114 antigen. In this study, we addressed the therapeutic potential of Kiatomab for treating both metastatic and solid tumors in mouse models. Kiatomab recognizes the linear epitope of KIAA1114, which is expressed on cell surfaces of various murine cancer cell lines. Kiatomab treatment induced potent antitumor responses in pulmonary metastasis models. Antitumor activity was mediated by the fragment crystallizable portion of Kiatomab and dependent on the host immune system. The use of Kiatomab alone as an antitumor therapy was ineffective in solid tumor models. However, in combination with cyclophosphamide, or by switching the isotype of the mAb, improved antitumor effects of Kiatomab were observed. These results suggest that Kiatomab can be used as a novel mAb for cancer immunotherapy.
基因KIAA1114的全长翻译产物是人类肝细胞癌中癌症干细胞的独特标志物,单克隆抗体Kiatomab对KIAA1114抗原具有特异性。在本研究中,我们探讨了Kiatomab在小鼠模型中治疗转移性肿瘤和实体瘤的潜力。Kiatomab识别KIAA1114的线性表位,该表位在多种鼠类癌细胞系的细胞表面表达。Kiatomab治疗在肺转移模型中诱导了强大的抗肿瘤反应。抗肿瘤活性由Kiatomab的可结晶片段介导,并依赖于宿主免疫系统。单独使用Kiatomab作为抗肿瘤疗法在实体瘤模型中无效。然而,与环磷酰胺联合使用,或通过切换单克隆抗体的同种型,可观察到Kiatomab的抗肿瘤效果得到改善。这些结果表明,Kiatomab可作为一种新型的癌症免疫治疗单克隆抗体。