Del Governatore M, Hamblin M R, Shea C R, Rizvi I, Molpus K G, Tanabe K K, Hasan T
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Cancer Res. 2000 Aug 1;60(15):4200-5.
Photoimmunotherapy (using a monoclonal antibody-targeted photosensitizer and red light) may be a strategy to overcome the limitations inherent in photodynamic therapy of liver tumors. The aims of this study were (a) to test the efficacy of selective treatment of hepatic metastases of colorectal cancer in an orthotopic murine xenograft using the murine monoclonal antibody 17.1A conjugated to the photosensitizer chlorin(e6), and (b) to compare the tumor response after the same light dose was delivered at two different fluence rates. Based on previous biodistribution studies that had shown that the photoimmunoconjugate with a polyanionic charge had both a higher absolute tumor chlorin(e6) content and a greater tumor:normal liver ratio than those obtained with a photoimmunoconjugate bearing a polycationic charge, mice were treated 3 h after i.v. injection of the polyanionic 17.1A chlorin(e6) conjugate or unconjugated photosensitizer. Red light was delivered into the liver tumor by an interstitial fiber, and tumor response end points were total tumor weight in the short term and survival in the long term. There was a highly significant reduction (<20% of controls; P = 0.0035) in the weight of the tumors in the mice treated with photoimmunotherapy, and the median survival increased from 62.5 to 102 days (P = 0.015). Photodynamic therapy with free chlorin(e6) produced a smaller decrease in tumor weight and a smaller extension of survival, neither of which were statistically significant. A comparison of photoimmunotherapy with 10 J of light delivered at 30 or 300 mW showed that the higher fluence rate prolonged survival significantly more than the lower fluence rate. This may have been because the high fluence rate gave a contribution of laser-induced hyperthermia to the photodamage. Correlation studies showed that the amount of normal liver remaining at necropsy correlated best with survival. Photoimmunotherapy shows efficacy in destroying liver tumors, and future studies should maximize selectivity to minimize the destruction of normal liver.
光免疫疗法（使用单克隆抗体靶向光敏剂和红光）可能是一种克服肝肿瘤光动力疗法固有局限性的策略。本研究的目的是：（a）在原位小鼠异种移植模型中，测试使用与光敏剂二氢卟吩（e6）偶联的鼠单克隆抗体17.1A选择性治疗结直肠癌肝转移的疗效；（b）比较在两种不同的光通量率下给予相同光剂量后肿瘤的反应。基于先前的生物分布研究表明，带聚阴离子电荷的光免疫偶联物比带聚阳离子电荷的光免疫偶联物具有更高的绝对肿瘤二氢卟吩（e6）含量和更大的肿瘤与正常肝脏比率，在静脉注射聚阴离子17.1A二氢卟吩（e6）偶联物或未偶联的光敏剂3小时后对小鼠进行治疗。通过间质光纤将红光导入肝肿瘤，肿瘤反应终点在短期内为肿瘤总重量，在长期内为生存率。接受光免疫疗法治疗的小鼠肿瘤重量显著降低（<对照组的20%；P = 0.0035），中位生存期从62.5天增加到102天（P = 0.015）。使用游离二氢卟吩（e6）的光动力疗法使肿瘤重量减少较小，生存期延长较小，两者均无统计学意义。对在30或300 mW下给予10 J光的光免疫疗法进行比较表明，较高的光通量率比低光通量率显著延长了生存期。这可能是因为高光通量率对光损伤有激光诱导的热疗作用。相关性研究表明，尸检时剩余的正常肝脏量与生存率的相关性最佳。光免疫疗法在破坏肝肿瘤方面显示出疗效，未来的研究应最大限度地提高选择性，以尽量减少对正常肝脏的破坏。
