Enhanced presentation of MHC class Ia, Ib and class II-restricted peptides encapsulated in biodegradable nanoparticles: a promising strategy for tumor immunotherapy

<p>Abstract</p> <p>Background</p> <p>Many peptide-based cancer vaccines have been tested in clinical trials with a limited success, mostly due to difficulties associated with peptide stability and delivery, resulting in inefficient antigen presentation. Therefore, the development of suitable and efficient vaccine carrier systems remains a major challenge.</p> <p>Methods</p> <p>To address this issue, we have engineered polylactic-co-glycolic acid (PLGA) nanoparticles incorporating: (i) two MHC class I-restricted clinically-relevant peptides, (ii) a MHC class II-binding peptide, and (iii) a non-classical MHC class I-binding peptide. We formulated the nanoparticles utilizing a double emulsion-solvent evaporation technique and characterized their surface morphology, size, zeta potential and peptide content. We also loaded human and murine dendritic cells (DC) with the peptide-containing nanoparticles and determined their ability to present the encapsulated peptide antigens and to induce tumor-specific cytotoxic T lymphocytes (CTL) <it>in vitro</it>.</p> <p>Results</p> <p>We confirmed that the nanoparticles are not toxic to either mouse or human dendritic cells, and do not have any effect on the DC maturation. We also demonstrated a significantly enhanced presentation of the encapsulated peptides upon internalization of the nanoparticles by DC, and confirmed that the improved peptide presentation is actually associated with more efficient generation of peptide-specific CTL and T helper cell responses.</p> <p>Conclusion</p> <p>Encapsulating antigens in PLGA nanoparticles offers unique advantages such as higher efficiency of antigen loading, prolonged presentation of the antigens, prevention of peptide degradation, specific targeting of antigens to antigen presenting cells, improved shelf life of the antigens, and easy scale up for pharmaceutical production. Therefore, these findings are highly significant to the development of synthetic vaccines, and the induction of CTL for adoptive immunotherapy.</p

The structural and dynamics neutron study of proton conductors: Difficulties and improvement procedures in protonated perovskite

With the expected development of Hydrogen as energy vector, there is a great impetus on the study of thermally stable proton conductors, the core of fuel cells, electrolysers and potential CO2 converters. Prior to a successful industrial application one should first well determine their extremely complex physical and chemical behaviour related to the unique character of the proton. The difficulties in comprehension of the nature of mobile protonic species, their location (especially the differentiation between bulk and surface species) as well as local and long range dynamics are different as a function of the hydration level: i) in hydrates the number of protons not really involved in the conduction is much larger than that of protonic conducting species, ii) in non-hydrated materials, the total amount of conducting protons can be very small, as dopants in semiconductors, and similar to that arising from surface water and physisorbed protonic moieties. The attempts and difficulties to locate and identify the protonic species and their dynamics using the neutron techniques are discussed in the light of representative examples, with emphasis on proton conducting perovskites