Liposomal delivery of CTL epitopes to dendritic cells.
The induction of strong and long lasting T-cell response, CD4+ or CD8+, is a major requirement in the development of efficient vaccines. An important aspect involves delivery of antigens to dendritic cells (DCs) as antigen presenting cells (APCs) for the induction of potent antigen-specific CD8+ T lymphocyte (CTLs) responses. Protein or peptide-based vaccines become an attractive alternative to the use of live cell vaccines to stimulate CTL responses for the treatment of viral diseases or malignancies. However, vaccination with proteins or synthetic peptides representing discrete CTL epitopes have failed in most instances due to the inability for exogenous antigens to be properly presented to T cells via major histocompatibility complex (MHC) class I molecules. Modern vaccines, based on either synthetic or natural molecules, will be designed in order to target appropriately professional APCs and to co-deliver signals able to facilitate activation of DCs. In this review, we describe the recent findings in the development of lipid-based formulations containing a combination of these attributes able to deliver tumor- or viral-associated antigens to the cytosol of DCs. We present in vitro and pre-clinical studies reporting specific immunity to viral, parasitic infection and tumor growth.
Chikh
Ghania
G
British Columbia Cancer Research Center, Dept of Advanced Therapeutics, Vancouver, Canada.
Schutze-Redelmeier
Marie-Paule
MP
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001105:Archaea / Q000737:chemistry; D002412:Cations; D003713:Dendritic Cells / Q000276:immunology*; D016503:Drug Delivery Systems; D000939:Epitopes / Q000008:administration & dosage* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D018398:Homeodomain Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008081:Liposomes; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification; D051379:Mice; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014157:Transcription Factors; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology
D000276:Adjuvants, Immunologic; D051943:Antennapedia Homeodomain Protein; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D002412:Cations; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D018398:Homeodomain Proteins; D008081:Liposomes; D008563:Membrane Lipids; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014157:Transcription Factors; D022223:Vaccines, Subunit; D011092:Polyethylene Glycols