Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial.

Background: Robust evidence supports the role of α-synuclein pathology as a driver of neuronal dysfunction in Parkinson's disease. PD01A is a specific active immunotherapy with a short peptide formulation targeted against oligomeric α-synuclein. This phase 1 study assessed the safety and tolerability of the PD01A immunotherapeutic in patients with Parkinson's disease.

Down-modulation of CXCR3 surface expression and function in CD8+ T cells from cutaneous T cell lymphoma patients.

Viruses can escape destruction by the immune system by exploitation of the chemokine-chemokine receptor system. It is less established whether human cancers can adopt similar strategies to evade immunologic control. In this study, we show that advanced cutaneous T cell lymphoma (CTCL) is associated with selective and efficient inactivation of CXCR3-dependent T cell migration.

Vaccination with prion peptide-displaying papillomavirus-like particles induces autoantibodies to normal prion protein that interfere with pathologic prion protein production in infected cells.

Prion diseases are fatal neurodegenerative disorders caused by proteinaceous infectious pathogens termed prions (PrP(Sc)). To date, there is no prophylaxis or therapy available for these transmissible encephalopathies. Passive immunization with monclonal antibodies recognizing the normal host-encoded prion protein (PrP(C)) has been reported to abolish PrP(Sc) infectivity and to delay onset of disease.

Identification of a de novo keratin 1 mutation in epidermolytic hyperkeratosis with palmoplantar involvement.

Epidermolytic hyperkeratosis (EHK) (OMIM 113800) is a generalized skin disease with mostly autosomal dominant inheritance, caused by mutations in keratin 1 or keratin 10. These genes are expressed in suprabasal epidermal layers, resulting in abnormal keratin-intermediate filament cytoskeleton. We present a male patient with generalized hyperkeratosis involving palms and soles.

Clusterin regulates drug-resistance in melanoma cells.

Clusterin has recently been shown to act as an antiapoptotic protein that confers drug-resistance in models of epithelial tumors. The aim of our work was to provide an insight into a possible role of clusterin in the regulation of drug-resistance in melanoma. In tissue samples, clusterin expression was low in nevi, but high in primary melanoma and melanoma metastases.

Balance between NF-kappaB and JNK/AP-1 activity controls dendritic cell life and death.

The life cycle of dendritic cells (DCs) must be precisely regulated for proper functioning of adaptive immunity. However, signaling pathways actively mediating DC death remain enigmatic. Here we describe a novel mechanism of hierarchical transcriptional control of DC life and death.

Definition of TCR epitopes for CTL-mediated attack of cutaneous T cell lymphoma.

Therapeutic vaccination against cutaneous T cell lymphoma (CTCL) requires the characterization of cancer cell-specific CTL epitopes. Despite reported evidence for tumor-reactive cytotoxicity in CTCL patients, the nature of the recognized determinants remains elusive. The clonotypic TCR of CTCL cells is a promising candidate tumor-specific Ag.