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HLA-A2.1–restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from β2 Microglobulin (β2m) HLA-A2.1 Monochain Transgenic H-2Db β2m Double Knockout Mice
TLDR
Three different HLA-A2.1 monochains were engineered in which either the human or mouse β2-microglobulin (β2m) is covalently linked to the NH2 terminus of the heavy chain by a 15– amino acid long peptide, and the selected HHD construct was introduced by transgenesis in H-2Db/− β2m−/− double knockout mice.
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Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes
TLDR
It is shown that dendritic cells derived from Rab27a-deficient ashen mice show increased phagosome acidification and antigen degradation, causing a defect in antigen cross-presentation.
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Complete DNA sequence of yeast chromosome XI
TLDR
The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined, and the 666,448-base-pair sequence has revealed general chromosome patterns.
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Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent
TLDR
It is shown here that this process, in the skin, can greatly be modulated according to the injection solution composition and blocked by an excess of competing nucleic acids or a drug affecting cytosolic mobility.
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Immunostimulating capacities of stabilized RNA molecules
TLDR
It is shown that mRNA molecules that are protected from immediate degradation either through interaction with cationic proteins (trans protection) or through chemical modification of the phosphodiester backbone (phosphorothioate RNA; cis protection) act as sequence‐independent danger signals on mouse DC.
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H‐2 class I knockout, HLA‐A2.1‐transgenic mice: a versatile animal model for preclinical evaluation of antitumor immunotherapeutic strategies
TLDR
HHD mice provide a versatile animal model for preclinical evaluation of peptide‐based cancer immunotherapy and CTL responses against five distinct epitopes could be elicited simultaneously in a single animal.
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Toll‐like receptor‐dependent activation of several human blood cell types by protamine‐condensed mRNA
TLDR
The data indicate that protamine‐stabilized RNA, which may be similar to RNA condensed in the nucleocapsids of RNA viruses, is a strong danger signal, and similarly to plasmid DNA, protamines‐RNA combines antigen production and non‐specific immunostimulation.
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A general strategy to enhance immunogenicity of low‐affinity HLA‐A2.1‐associated peptides: implication in the identification of cryptic tumor epitopes
TLDR
P1Y substitution enhances affinity of HLA‐A2.1‐associated peptides without altering their antigenic specificity and provides the necessary tool for the identification of cryptic tumor and virus epitopes which could be used for peptide‐based immunotherapy.
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Direct Injection of Protamine-protected mRNA: Results of a Phase 1/2 Vaccination Trial in Metastatic Melanoma Patients
TLDR
It is shown here that direct injection of protamine-protected mRNA is feasible and safe and the significant influence of the treatment on the frequency of immunosuppressive cells, the increase of vaccine-directed T cells upon treatment in a subset of patients together with the demonstration of a complete clinical response encourage further clinical investigation of the protamines-mRNA vaccine.
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Results of the First Phase I/II Clinical Vaccination Trial With Direct Injection of mRNA
TLDR
It is demonstrated here that such treatment is feasible and safe (phase 1 criteria) and an increase in antitumor humoral immune response was seen in some patients, however, a demonstration of clinical effectiveness of direct injection of copy mRNA for antitumors immunotherapy was not shown in this study and must be evaluated in subsequent trials.
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