Genetically engineered dendritic cell-based cancer vaccines (review).
Dendritic cells (DCs) are the most potent professional antigen-presenting cells with exquisite capacity to interact with T cells and initiate their responses; the antigen-presenting capabilities of DCs make them attractive vehicles for the delivery of therapeutic cancer vaccines. The working hypothesis for utilization of DC-based cancer vaccines is that lack of efficient tumour antigen presentation on mature DCs, which is frequently observed in tumour-bearing individuals, can be bypassed by direct loading of DCs with oncoproteins in vitro, thus ensuring the transfer of immunostimulatory peptides on the respective antigen-presenting molecules. To enhance loading of DCs with oncoproteins in vitro and to increase the efficacy of the vaccines, a variety of genetic manipulations have been proposed and shown to be efficient in experimental tumour models. DCs were transfected either with polynucleotides, DNA or RNA, coding for tumour-associated antigens (TAAs), or with DNA encoding immunostimulatory cytokines and co-stimulatory molecules. The delivery of genes coding for antigenic epitopes or other molecules with a recombinant retrovirus, adenovirus, or poxvirus into dendritic cells has also been used for transduction and therapy. As an alternative method for TAA delivery into DCs, fusion of DCs with tumour cells has been utilized and the hybrid cell-based vaccines have been found to be highly therapeutically active, even in cancer patients. The purpose of this review is to summarize the approaches used for making and utilization of the genetically engineered DC-based cancer vaccines, to evaluate the therapeutic results obtained with the vaccines, and to discuss prospects and limitations of the vaccination.
Bubeník
J
J
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic. bubenik@img.cas.cz
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology; D002986:Clinical Trials as Topic; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D018014:Gene Transfer Techniques; D005818:Genetic Engineering / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D011119:Polynucleotides / Q000378:metabolism*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004279:DNA, Viral; D011119:Polynucleotides