Peptide/protein based vaccines To date, several peptide-based vaccines are either undergoing clinical evaluation or are in development. A major limitation to peptide-based vaccines is the need to identify the immunogenic epitope of the tumour-associated antigen. The observation that the antigenic epitope with the highest binding affinity to the HLA molecule does not necessarily correlate with CH5183284 mouse its potential immunogenicity in vivo decreases the applicability of these peptide

based vaccines. Thus, MHC molecules may restrict the candidacy for this approach, making difficult to carry out large scale vaccination treatment schemes. The HLA restriction associated with peptide-based vaccines can be overcome with the use of whole protein-based vaccines, harbouring multiple immunogenic epitopes which can bind the various allelic HLA molecules. However, due to the poor immunogenicity of both peptides and proteins most of the researches in this area have focused on the Ro 61-8048 supplier co-administration of adjuvant immune-enhancing agents such as chemokines, cytokines, and costimulatory

molecules to enhance the potency of the vaccine [for a review, see [3, 23]]. Chimeric GM-CSF molecules can enhance antigenic immune responses through the recruitment of antigen present cells [24, 25]; co-administration of immunostimulatory CpG oligodeoxynucleotides may be able to stimulate macrophages to secrete IL-12 shifting the cytokine profiles to a Th1-type cell-mediated immune response [26, PSI-7977 order 27]. Recently the fusion of the beta-1,3–1,4-glucanase (LicKM) of Clostridium thermocellum bacterial protein to the HPV E7 protein produced an antigen with strong intrinsic adjuvating activity, indicating that manipulation of the antigen may elicit some unknown helpful function [28, 29] The results of clinical trials indicate that peptide/protein vaccination has low toxicity but a strong Rolziracetam discordance exists

between immune and clinical responses, reinforcing the need of further improvement to the vaccination by the utilization of peptide-pulsed dendritic cells, the addition of helper peptides, and depletion of Treg. Several phase I clinical trials using antigenic peptides derived from HPV E6/E7 have been so far conducted as well as multivalent peptide-based vaccination against p53 [30–32] with only “”promising”" vaccine-induced immunologic responses. DNA/RNA based DNA vaccines have been used in the clinical arena to elicit antigen-specific immune responses. Although nucleic acid vaccines do not appear to induce as vigorous immune responses as live viral vaccine vectors, they have several advantages. Naked DNA is relatively safe, stable, cost efficient, and able to sustain reasonable levels of antigen expression within cells [for review see [33, 34]] DNA-based plasmid vectors remain stable in a wide range of conditions over great lengths of time, and they can be delivered with little risk to individuals who are immunosuppressed.