Mizukami Makiko, Hanagiri Takeshi, Baba Tetsuro, Fukuyama Takashi, Nagata Yoshika, So Tetsuya, Ichiki Yoshinobu, Sugaya Masakazu, Yasuda Manabu, Takenoyama Mitsuhiro, Sugio Kenji, Yasumoto Kosei
Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Cancer Sci. 2005 Dec;96(12):882-8. doi: 10.1111/j.1349-7006.2005.00119.x.
We previously demonstrated that TIB recognize tumor antigens and produce antibodies against them. In the present study, we identified three tumor antigens recognized by TIB in lung cancer and evaluated whether changes in the antibody titer against these antigens correlated with the patient's clinical course. A lung cancer cell line, G603L, was established from a primary lung tumor of a patient, G603. Seven months later, adrenal metastasis was detected and surgically resected. The latter tumor was mildly infiltrated with B cells and xenotransplanted into SCID mice to obtain human IgG. A cDNA library was constructed from G603L and SEREX was carried out using TIB-derived IgG. The sero-reactive clones were sequenced and one of these antigens was revealed to be MAGE-B2 whereas the others were novel antigens. In the immuno-monitoring of the patient's sera, high antibody titer against MAGE-B2 was observed before operation and the titer decreased after resection of the primary tumor. It was elevated again at the time of adrenal metastasis, but then decreased after resection. The change in antibody titer against the second antigen was similar to MAGE-B2, and the antibody titer against the third antigen was low before the primary operation but increased at the time of recurrence. Our results suggest that TIB recognized tumor antigens and the antibody titers against these antigens were changed along with the patient's clinical course. Therefore, these antibodies could be used as tumor markers for the patient.
我们之前证明了肿瘤浸润性B细胞（TIB）能够识别肿瘤抗原并产生针对这些抗原的抗体。在本研究中，我们鉴定了TIB在肺癌中识别的三种肿瘤抗原，并评估了针对这些抗原的抗体滴度变化是否与患者的临床病程相关。肺癌细胞系G603L是从患者G603的原发性肺肿瘤中建立的。七个月后，检测到肾上腺转移并进行了手术切除。后一个肿瘤有轻度B细胞浸润，并异种移植到SCID小鼠中以获得人IgG。从G603L构建cDNA文库，并使用TIB来源的IgG进行血清学表达克隆筛选（SEREX）。对血清反应性克隆进行测序，其中一种抗原被鉴定为MAGE - B2，而其他则是新抗原。在对患者血清的免疫监测中，术前观察到针对MAGE - B2的高抗体滴度，原发性肿瘤切除后滴度下降。在肾上腺转移时再次升高，但切除后又下降。针对第二种抗原的抗体滴度变化与MAGE - B2相似，针对第三种抗原的抗体滴度在原发性手术前较低，但在复发时升高。我们的结果表明，TIB识别肿瘤抗原，并且针对这些抗原的抗体滴度随患者的临床病程而变化。因此，这些抗体可作为该患者的肿瘤标志物。
