Cancer immunotherapy with mRNA-transfected dendritic cells.
Bone marrow-derived dendritic cells (DCs) are the most potent antigen-presenting cells capable of activating naïve T cells. Loading DCs ex vivo with tumor antigens can stimulate potent antitumor immunity in tumor-bearing mice. This review describes the use of mRNA-encoded tumor antigens as a form of antigen loaded onto DCs, including our early experience from clinical trials in urological cancers. Transfection of DCs with mRNA is simple and effective. Comparative studies suggest that mRNA transfection is superior to other antigen-loading techniques in generating immunopotent DCs. The ability to amplify RNA from microscopic amounts of tumor tissue extends the use of DC vaccination to virtually every cancer patient. The striking observation from two phase I clinical trials, in patients with prostate cancer immunized with prostate-specific antigen mRNA-transfected DCs and patients with renal cancer immunized with autologous tumor RNA-transfected DCs, was that the majority of patients exhibited a vaccine-induced T-cell response. Suggestive evidence of clinically related responses was seen in both the trials. Immunization with mRNA-transfected DCs is a promising strategy to stimulate potent antitumor immunity and could serve as a foundation for developing effective treatments for cancer.
Gilboa
Eli
E
Department of Surgery, Center for Genetic and Cellular Therapies, Duke University Medical Center, Durham, NC 27710, USA. e.gilboa@cgct.duke.edu
Vieweg
Johannes
J
D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000379:methods
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen