van Dongen G A M S, Visser G W M, Vrouenraets M B
Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Adv Drug Deliv Rev. 2004 Jan 13;56(1):31-52. doi: 10.1016/j.addr.2003.09.003.
Photodynamic therapy (PDT) is a promising approach for the treatment of superficially localized tumors. A limitation, however, is the lack of selectivity of the photosensitizers, which can result in severe toxicity. In this overview, the possibilities for using monoclonal antibodies (MAbs) for selective delivery of photosensitizers to tumors, are discussed. This approach is called photoimmunotherapy (PIT). For PIT to be successful, sufficient amounts of sensitizer should be coupled to the MAb without altering its biological properties. A challenging aspect herein is the hydrophobicity of therapeutic photosensitizers. Options for direct and indirect coupling of photosensitizers to MAbs are evaluated, while pros and cons are indicated. Special attention is paid to the quality testing of photoimmunoconjugates, as this information is important for further optimization of PIT. Results obtained thus far with PIT in in vitro and in vivo model systems are discussed. Despite the encouraging progress made, showing the high selectivity of photoimmunoconjugates, PIT still awaits initial clinical evaluation.
光动力疗法(PDT)是一种治疗浅表局限性肿瘤的很有前景的方法。然而,一个局限性是光敏剂缺乏选择性,这可能导致严重的毒性。在本综述中,讨论了使用单克隆抗体(MAb)将光敏剂选择性递送至肿瘤的可能性。这种方法称为光免疫疗法(PIT)。为使PIT成功,应将足够量的敏化剂偶联到单克隆抗体上,同时不改变其生物学特性。其中一个具有挑战性的方面是治疗性光敏剂的疏水性。评估了光敏剂与单克隆抗体直接和间接偶联的选择,并指出了优缺点。特别关注光免疫偶联物的质量检测,因为这些信息对于进一步优化PIT很重要。讨论了迄今为止在体外和体内模型系统中使用PIT获得的结果。尽管取得了令人鼓舞的进展,显示了光免疫偶联物的高选择性,但PIT仍有待初步临床评估。