Preparation, phototoxicity and biodistribution studies of anti-carcinoembryonic antigen monoclonal antibody-phthalocyanine conjugates
Preparation, phototoxicity and biodistribution studies of anti-carcinoembryonic antigen monoclonal antibody-phthalocyanine conjugates
复制标题
DOI：
10.1111/j.1751-1097.1999.tb08304.x
复制
发表时间：
1999-12-01
影响因子：
3.3
通讯作者：
Pèlegrin, A
中科院分区：
文献类型：
--
作者：
Carcenac, M;Larroque, C;Pèlegrin, A
癌症的免疫光疗结合了单克隆抗体（MAb）对过表达肿瘤标记物的特异性和偶联染料的光毒性。四硫眼青碱铝（AlPcS4）通过一个五碳间隔链（a(1)）与一个针对癌胚抗原（CEA）的35A7单抗共价偶联，得到的偶联物的摩尔比为5 ~ 16 mol / mel 35A7单抗。用放射性碘标记缀合物进行表征。偶联物的免疫反应性，通过CEA与sepharose的直接结合实验来确定，被偶联的AlPcS(4) a(1)分子净修饰。在体内，这些偶联物在携带人类结肠癌异种移植物（T380）的裸鼠中进行了评估，35A7 MAb-(AlPcS(4)A(1))(5)、35A7 MAb-(AlPcS(4)A(1))（12）和35A7 MAb-(AlPcS(4)A(1))（16）偶联物的肿瘤摄取分别为每克肿瘤组织注射剂量的35 +/- 5.0%、40 +/- 5.7%和32 +/- 3.3%，与未偶联的35A7 MAb相比，其摄取分别为97%、104%和91%。在每个实验组中，结合物获得的肿瘤与正常组织的比例几乎与未结合的35A7单抗获得的比例相同。血液、肝脏和肌肉的平均值分别为1.8、7和30左右。35A7 MAb-(AlPcS(4)A(1))（12）偶联物在体外对LoVo细胞系的光毒作用得到了证明，当AlPcS4A(1)浓度为2.50 μ g/mL时，其生长抑制率为91%。我们得出结论，这些缀合物在体内表现出明确的肿瘤寻找能力和体外光细胞毒性。因此，这些缀合物可能是表达CEA的癌症的临床光动力治疗的有希望的候选药物。
Immunophototherapy of cancer combines the specificity of a monoclonal antibody (MAb) to an overexpressed tumor marker with the phototoxic properties of a conjugated dye. Aluminum tetrasulfophthalocyanine (AlPcS4) was covalently coupled to a 35A7 MAb directed against carcinoembryonic antigen (CEA) via a five-carbon spacer chain (A(1)) to yield conjugates with a molar ratio ranging from 5 to 16 mol of AlPcS4 per mel of 35A7 MAb. Conjugates were labeled with radioiodine for characterization. The immunoreactivity of the conjugates, determined in a direct binding assay on CEA coupled to sepharose, was net modified by the coupled AlPcS(4)A(1) molecules. In vivo, these conjugates were evaluated in nude mice bearing human colon carcinoma xenografts (T380), 35A7 MAb-(AlPcS(4)A(1))(5), 35A7 MAb-(AlPcS(4)A(1))(12) and 35A7 MAb-(AlPcS(4)A(1))(16) conjugates displayed a tumor uptake of 35 +/- 5.0%, 40 +/- 5.7% and 32 +/- 3.3% of the injected dose per gram of tumor tissue, respectively, corresponding to an uptake of 97%, 104% and 91% as compared to that of the unconjugated 35A7 MAb. In each experimental group, the tumor-to-normal tissue ratios obtained with the conjugates were almost identical to those obtained with unconjugated 35A7 MAb. Average values of 1.8, 7 and about 30 were obtained for blood, liver and muscle, respectively. Phototoxic efficacy of the 35A7 MAb-(AlPcS(4)A(1))(12) conjugate was demonstrated in vitro on the LoVo cell line giving a 91% growth inhibition for a 2.50 mu g/mL AlPcS4A(1), concentration. We conclude that these conjugates demonstrate clear in vivo tumor-seeking capacity and in vitro photocytotoxic properties. Such conjugates could thus be promising candidate drugs for clinical photodynamic therapy of cancers expressing CEA.