Murthy Vedang, Moiyadi Aliasgar, Sawant Rajesh, Sarin Rajiv
Department of Radiation Oncology and Cancer Genetics, Advanced Center for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India.
Curr Mol Med. 2009 Aug;9(6):725-31. doi: 10.2174/156652409788970689.
Since the first reported clinical trial of Dendritic Cell Vaccine (DCV) in cancer in the mid nineties, few hundred clinical trials have been initiated and it was projected that over 3000 patients would be treated in DCV clinical trials by 2008. Despite extensive data to establish its safety, DCV remains an investigational approach, highlighting the need to undertake more meaningful proof of principle studies and more importantly, well designed and well conducted large efficacy trials. As opposed to phase I and II trials of new chemical entities where pharmacokinetics, maximum tolerated dose, toxicity profile and dose response effects are the primary concerns, for DCV the pertinent issues are quite different. Based on a critical appraisal of the available literature, we examine the important host, tumour and treatment considerations and specific issues related to the design and conduct of DCV based clinical trials. Impact of patient related factors such as extremes of age, host immune competence and the host HLA type on the host immune response to DCV and using these parameters either as a selection criteria or a stratification parameter is discussed. Clinical trials of DCV also need to consider selection of tumour types and their antigenic expression better suited for DCV. The influence of previous or concurrent cytotoxic treatment and corticosteroid which could influence the yield of monocytes in leukapheresis or the host immune response to DCV requires consideration in the clinical trial design. Safety issues of DCV in pregnant women, children and in those with inherent of acquired immune disorders are discussed.
自上世纪九十年代中期首次报道树突状细胞疫苗（DCV）用于癌症的临床试验以来，已经启动了数百项临床试验，预计到2008年将有超过3000名患者接受DCV临床试验。尽管有大量数据证明其安全性，但DCV仍然是一种试验性方法，这突出表明需要进行更有意义的原理验证研究，更重要的是，需要设计良好且实施得当的大型疗效试验。与新化学实体的I期和II期试验不同，新化学实体试验主要关注药代动力学、最大耐受剂量、毒性特征和剂量反应效应，而对于DCV来说，相关问题则大不相同。基于对现有文献的批判性评估，我们审视了重要的宿主、肿瘤和治疗方面的考虑因素，以及与基于DCV的临床试验设计和实施相关的具体问题。讨论了患者相关因素，如年龄极端情况、宿主免疫能力和宿主HLA类型对宿主对DCV免疫反应的影响，以及将这些参数用作选择标准或分层参数的情况。DCV的临床试验还需要考虑选择更适合DCV的肿瘤类型及其抗原表达。在临床试验设计中需要考虑先前或同时进行的细胞毒性治疗和皮质类固醇的影响，它们可能会影响白细胞分离术中单核细胞的产量或宿主对DCV的免疫反应。还讨论了DCV在孕妇、儿童以及患有先天性或获得性免疫疾病患者中的安全性问题。
