Desrues B, Brichory F, Léna H, Bourguet P, Delaval P, Toujas L, Dazord L
Centre Hospitalier Regional et Universitaire, Hôpital Pontchaillou, Rennes, France.
Cancer Immunol Immunother. 1996 Dec;43(5):269-74. doi: 10.1007/s002620050333.
Po66, a mouse monoclonal antibody, is directed against an intracytoplasmic antigen present in human lung squamous cell carcinoma cells. In previous work it was found that the co-administration of 125I-radiolabelled Po66 and doxorubicin strongly enhanced the uptake of radioactivity by the tumour. The present-work was designed to evaluate, in a tumour-bearing mouse model of lung carcinoma, the ability of 131I-labelled Po66 to retard tumour growth when injected alone, or in combination with doxorubicin (8 mg kg-1 at 1-week intervals). A single dose of 550 microCi 131I-Po66 alone had no effect on tumour growth, whereas three fractionated doses of 250 microCi 131I-Po66 decreased it over two doubling times from 14.5 +/- 1.5 days for untreated control mice to 24.8 +/- 2.7 days. Mice treated with doxorubicin alone had a double tumour doubling time of 22.6 +/- 4.9 days, compared to 35.2 +/- 2.9 days (1.55-fold increase) in mice treated with doxorubicin and a single dose of 550 microCi 131I-Po66. Doxorubicin combined with three fractionated doses of 250 microCi 131I-Po66 provoked a twofold decrease in tumour growth compared to mice treated with doxorubicin alone. The administration of fractionated doses of 131I-Po66 simultaneously with doxorubicin resulted in a highly delayed mortality, which was not observed when 131I-Po66 was administered after doxorubicin. Thus, in a non-small-cell lung tumour model, a 131I-radiolabelled monoclonal antibody, directed against an intracellular antigen, significantly potentiated the effect of chemotherapy. Such a therapeutic approach could be used as an adjuvant therapy and improve the effect of chemotherapy on distant small metastases.
Po66是一种小鼠单克隆抗体，可靶向人肺鳞状细胞癌细胞内的一种胞浆抗原。在之前的研究中发现，125I标记的Po66与阿霉素联合使用可显著增强肿瘤对放射性的摄取。本研究旨在评估在荷瘤肺癌小鼠模型中，单独注射131I标记的Po66或与阿霉素（8 mg/kg，间隔1周）联合使用时，其抑制肿瘤生长的能力。单独单次注射550 μCi 131I-Po66对肿瘤生长无影响，而分三次注射250 μCi 131I-Po66可使肿瘤倍增时间从未治疗对照小鼠的14.5±1.5天延长至24.8±2.7天，延长了两倍多。单独使用阿霉素治疗的小鼠肿瘤倍增时间为22.6±4.9天，而联合使用阿霉素和单次注射550 μCi 131I-Po66的小鼠肿瘤倍增时间为35.2±2.9天（增加了1.55倍）。与单独使用阿霉素治疗的小鼠相比，阿霉素联合分三次注射250 μCi 131I-Po66可使肿瘤生长减少两倍。131I-Po66与阿霉素同时分剂量给药导致死亡高度延迟，而在阿霉素给药后给予131I-Po66则未观察到这种情况。因此，在非小细胞肺癌模型中，一种针对细胞内抗原的131I标记单克隆抗体可显著增强化疗效果。这种治疗方法可作为辅助治疗，提高化疗对远处小转移灶的疗效。
