Clinical considerations in developing dendritic cell vaccine based immunotherapy protocols in cancer.

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.