Genetically modified dendritic cells--a new, promising cancer treatment strategy?
Dendritic cells (DCs), the most potent antigen-presenting cells (APCs), were discovered almost 30 years ago. Due to the priming of antigen-specific immune responses mediated by CD4+ and CD8+ lymphocytes, DCs are crucial for the induction of adaptive immunity against cancer. Therefore, vaccination of cancer patients with DCs presenting tumour-associated antigens (TAAs) have been believed to be a promising anticancer strategy. Multiple clinical trials have been carried out in order to evaluate the safety and efficacy of cancer vaccines based on antigen-pulsed DCs. However, pulsing of DCs with particular peptides has several disadvantages: i) short-time duration of antigen-major histocompatability complex (MHC) complexes, ii) a requirement for matching defined peptides with MHC complexes and iii) exclusive presentation of single antigen epitopes. Application of gene transfer technologies in the field of DC-based vaccines made possible the development of novel, anticancer immunisation strategies. In several animal models, DCs modified with genes encoding TAA or immunostimulatory proteins have been shown to be effective in the induction of antitumour immune responses. Based on these encouraging results, a first clinical trial of prostate cancer patients vaccinated with gene modified DCs has recently been initiated. In this article, methods used for genetic modification of DCs and anticancer vaccination strategies based on genetically modified DCs are reviewed.
Wysocki
P J
PJ
Department of Cancer Immunology, University School of Medical Sciences at GreatPoland Cancer Centre, Poznan, Poland. pwysocki@plusnet.pl
Grabarczyk
P
P
Mackiewicz-Wysocka
M
M
Kowalczyk
D W
DW
Mackiewicz
A
A
D000818:Animals; D003713:Dendritic Cells / Q000502:physiology* / Q000637:transplantation*; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000628:therapy*