-
利用放射性核素标记单克隆抗体(monoclonal antibody,McAb)对肿瘤进行放射免疫治疗(radioimmunotherapy,RIT)的方法,具有靶向性好、病灶区局部核素浓聚度高的优点,对肿瘤细胞的选择性杀伤优于放疗和化疗,并可同时通过放射免疫显像(radioimmunoimaging,RII)进行诊断和监测[1],是核医学科的重要发展方向和临床肿瘤治疗的重要补充手段[2]。传统的RIT利用McAb识别肿瘤细胞表面的肿瘤相关抗原,在B细胞恶性肿瘤特别是B细胞非霍奇金淋巴瘤的治疗中具有显著的疗效,但对实体瘤的治疗疗效仍不理想[3]。
传统的RIT治疗实体瘤的困难,包括正常组织靶抗原的表达、循环抗原的存在、抗原调变和肿瘤摄取率低等方面[4]。为了解决上述问题,一种以肿瘤的坏死区域为靶目标的新方法被用于实体瘤的治疗研究中,称为肿瘤坏死疗法(tumor necrosis treatment,TNT)。这种方法是基于大多数实体瘤内部存在较高比例的变性和坏死细胞,以McAb为载体,识别实体瘤坏死区内暴露的细胞内抗原,从而达到治疗的目的[4]。131I-肿瘤细胞核人鼠嵌合单克隆抗体(131I labeled human-mouse chimeric tumor necrosis therapy monoclonal antibody,131I-chTNT)规避了传统RIT中膜抗原McAb仅表达少数肿瘤的局限,其靶抗原广泛存在于细胞核中[5]。因此,131I-chTNT能与各种肿瘤坏死区的细胞核特异性结合,从而实现对多种实体瘤进行有效治疗。
131I-肿瘤细胞核人鼠嵌合单克隆抗体治疗实体瘤的研究进展
Advances on the treatment of solid tumor by 131I labeled mouse-human chimeric tumor necrosis therapy monoclanal antibody
-
摘要: 131I-肿瘤细胞核人鼠嵌合单克隆抗体(131I-chTNT)以肿瘤的坏死区域为靶目标,因其靶抗原广泛存在于细胞核中,突破了传统放射免疫治疗中核素标记的单克隆抗体仅能以肿瘤细胞表面抗原为靶向的局限性,从而可实现对肺癌、肝癌、大肠癌及神经胶质瘤等多种实体瘤的有效治疗。131I-chTNT与现有放、化疗及射频消融方法等联合应用,可增加肿瘤坏死区域,暴露更多结合靶点,使131I-chTNT治疗实体瘤取得更好的疗效。Abstract: 131I labeled mouse-human chimeric tumor necrosis therapy monoclonal antibody(131I-chTNT) is a kind of new drug targeting at degenerated or necrotic nuclei in the tumor necrosis zone, and may be applicable to the majority of human solid tumors, such as lung cancer, liver cancer, colon carcinoma and glioma, while conventional tumor cell monoclonal antibody can target only tumor cell surface antigen. Enhanced effects can be achieved by 131I-chTNT in combination with other therapies, such as radiotherapy, chemotherapy or radiofrequency ablation, which may increase tumor necrosis region and expose more combinative targets.
-
Key words:
- Antibodies, monoclonal /
- Indine radioisotopes /
- Neoplasms /
- Radioimmunotherapy
-
[1] Börjesson PK, Postema EJ, de Bree R, et al. Radioimmunodetection and radioimmunotherapy of head and neck cancer. Oral Oncol, 2004, 40(8): 761-772. [2] Lin FI, Iagaru A. Current concepts and future directions in radioimmunotherapy. Curr Drug Discov Technol, 2010, 7(4): 253-262. [3] Song H, Sgouros G. Radioimmunotherapy of solid tumors: searching for the right target. Curr Drug Deliv, 2011, 8(1): 26-44. [4] Epstein AL, Khawli LA, Chen FM, et al. Tumor necrosis imaging and treatment of solid tumors//Torchilin VP. Handbook of targeted delivery of imaging agents. Boca Raton: CRC Press, 1995: 259-288. [5] Shapiro WR, Carpenter SP, Roberts K, et al. 131I-chTNT-1/B mAb: tumour necrosis therapy for malignant astrocytic glioma. Expert Opin Biol Ther, 2006, 6(5): 539-545. [6] Yu L, Ju DW, Chen W, et al. 131I-chTNT radioimmunotherapy of 43 patients with advanced lung cancer. Cancer Biother Radiopharm, 2006, 21(1): 5-14. doi: 10.1089/cbr.2006.21.5 [7] Srivastava S, Dadachova E. Recent advances in radionuclide therapy. Semin Nucl Med, 2001, 31(4): 330-341. [8] Cooper EH. The biology of cell death in tumours. Cell Tissue Kinet, 1973, 6(1): 87-95. [9] Aarts F, Bleichrodt RP, Oyen WJ, et al. Intracavitary radioimmunotherapy to treat solid tumors. Cancer Biother Radiopharm, 2008, 23(1): 92-107. doi: 10.1089/cbr.2007.0412 [10] 陈仰纯, 陈绍亮, 鞠佃文, 等. 131碘肿瘤细胞核人鼠嵌合单抗药代动力学研究.中国药科大学学报, 2004, 35(2): 164-167. doi: 10.3321/j.issn:1000-5048.2004.02.016
[11] 张浩然, 马庆杰, 赵劼, 等. 131I-chTNT在分化型甲状腺癌肺转移患者体内的生物学分布.中国老年学杂志, 2009, 29(1): 65-67. doi: 10.3969/j.issn.1005-9202.2009.01.029
[12] Hornick JL, Sharifi J, Khawli LA, et al. Single amino acid substitution in the Fc region of chimeric TNT-3 antibody accelerates clearance and improves immunoscintigraphy of solid tumors. J Nucl Med, 2000, 41(2): 355-362. [13] Kraeber-Bodéré F, Rousseau C, Bodet-Milin C, et al. Targeting, toxicity, and efficacy of 2-step, pretargeted radioimmunotherapy using a chimeric bispecific antibody and 131I-labeled bivalent hapten in a phase I optimization clinical trial. J Nucl Med, 2006, 47(2): 247-255. [14] Chen S, Yu L, Jiang C, et al. Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer. J Clin Oncol, 2005, 23(7): 1538-1547. [15] 杜阳峰, 罗荣城, 李贵平, 等.抗乙型肝炎表面抗原Fab片段联合抗细胞核单抗为载体的肝癌放射免疫治疗实验研究.南方医科大学学报, 2008, 28(3): 460-462. doi: 10.3321/j.issn:1673-4254.2008.03.031
[16] 罗荣城, 李爱民, 廖旺军, 等.核素标记不同性质单抗瘤内注射治疗大肠癌的研究.中国肿瘤生物治疗杂志, 2001, 8(4): 257-259. doi: 10.3872/j.issn.1007-385X.2001.04.005
[17] 傅相平, 李安民, 张志文, 等. 131I-肿瘤细胞核人鼠嵌合单抗脑胶质瘤瘤内放免治疗研究.中华实验外科杂志, 2005, 22(1): 102-103. doi: 10.3760/j.issn:1001-9030.2005.01.040
[18] Epstein AL, 王静.放射免疫治疗的若干进展.中华核医学杂志, 2007, 27(1): 60-62. doi: 10.3760/cma.j.issn.2095-2848.2007.01.028
[19] Vignaud JM, Ménard O, Weinbreck N, et al. Evaluation of the spatial diffusion of methylene blue injected in vivo by bronchoscopy into non-small cell lung carcinoma. Respiration, 2006, 73(5): 658-663. [20] Khawli LA, Mizokami MM, Sharifi J, et al. Pharmacokinetic characteristics and biodistribution of radioiodinated chimeric TNT-1, -2, and-3 monoclonal antibodies after chemical modification with biotin. Cancer Biother Radiopharm, 2002, 17(4): 359-370. [21] McTaggart RA, Dupuy DE. Thermal ablation of lung tumors. Tech Vasc Interv Radiol, 2007, 10(2): 102-113. [22] 韦青, 赵晟. 131I-chTNT放射免疫联合微波消融术综合治疗晚期肺癌.中国误诊学杂志, 2011, 11(6): 1278-1280.
[23] 王凯, 孙业全, 王丽英, 等.氩氦刀联合131I-chTNT放射免疫治疗中晚期非小细胞肺癌的疗效观察.国际医学放射学杂志, 2012, 35(3): 211-215. doi: 10.3784/j.issn.1674-1897.2012.03.10302
计量
- 文章访问数: 2028
- HTML全文浏览量: 866
- PDF下载量: 2