Phase I trial of viral vector based personalized vaccination elicits robust neoantigen specific antitumor T cell responses

Purpose: Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T cell response to overcome tumor heterogeneity. NOUS-PEV is a vector based personalized vaccine, expressing 60 nAgs and consists of priming with a non-human Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara (MVA). Here, we report data of a phase Ib trial of NOUS-PEV in combination with pembrolizumab in treatment naïve metastatic melanoma patients (NCT04990479). Experimental Design: The feasibility of this approach was demonstrated by producing, releasing and administering to six patients 11 out of 12 vaccines within 8 weeks from biopsy collection to GAd20 administration. Results: The regimen was safe, with no treatment-related serious adverse events observed and mild vaccine-related reactions. Vaccine immunogenicity was demonstrated in all evaluable patients receiving the prime/boost regimen, with detection of robust neoantigen specific immune responses to multiple neoantigens comprising both CD4 and CD8 T cells. Expansion and diversification of vaccine-induced TCR clonotypes was observed in the post-treatment biopsies of patients with clinical response providing evidence of tumor infiltration by vaccine-induced neoantigen-specific T cell. Conclusions: These findings indicate the ability of NOUS-PEV to amplify and broaden the repertoire of tumor reactive T cells to empower a diverse, potent and durable antitumor immune response. Finally, a gene signature indicative for reduced presence of activated T cells together with very poor expression of the antigen processing machinery (APM) genes has been identified in pre-treatment biopsies as a potential biomarker of resistance to the treatment

Multisystem inflammatory syndrome in children in western countries: decreasing incidence as the pandemic progresses? An observational multicenter international cross-sectional study

Multisystemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children (MIS-C) has been reported worldwide.1–7 The case definition of MIS-C has been estab- lished by different institutions and organizations such as the US Centers for Disease Control and Prevention (CDC) (May 14, 2020),8 the Royal College of Paediatrics and Child Health in the United Kingdom (RCPCH) (May 1, 2020)9,10 and the World Health Organi- zation (WHO) (May 15, 2020).1Postprint (published version

Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour

<p>Abstract</p> <p>Background</p> <p>Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters.</p> <p>Methods</p> <p>The validation assay was performed in a different set of 8 patients with colorectal cancer (CRC) by means quantitative reverse-transcriptase polymerase chain reaction analysis. The differential RNA expression profiles of three CRC cell lines before and after 5-aza-2'-deoxycytidine treatment were compared to identify the hypermethylated genes. The DNA methylation status of these genes was evaluated by means of bisulphite genomic sequencing and methylation-specific polymerase chain reaction (MSP) in the 3 cell lines and in tumour tissues from 30 patients with CRC.</p> <p>Results</p> <p>Data from our previous genome search have received confirmation in the new set of 8 patients with CRC. In this validation set six genes showed a high induction after drug treatment in at least two of three CRC cell lines. Among them, the N-myc downstream-regulated gene 2 (<it>NDRG2) </it>promoter was found methylated in all CRC cell lines. <it>NDRG2 </it>hypermethylation was also detected in 8 out of 30 (27%) primary CRC tissues and was significantly associated with advanced AJCC stage IV. Normal colon tissues were not methylated.</p> <p>Conclusion</p> <p>The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage.</p

Pompei. L'Insula Occidetalis. Indagini e riletture

The archaeological investigations carried out in Pompeii belong to a cooperation agreement between the Archaeological Park of Pompeii and the University of Naples Federico II. The research programme focuses on a sector of the so-called Insula Occidentalis, close to the Herculaneum Gate. The project aims to recompose, first of all, the dossier of archival sources related to the Bourbon excavations. The “archaeology of the buried “and the “archaeology of built” characterise the analysis of the almost completely unpublished buildings. We present, on this occasion, the first results of research in the Casa del Leone (VI 17, ins. occ., 23-25) and the Hospitium of Albinus (VI 17 ins. occ., 1-4). The analysis of the Hospitium allowed to recognize an interesting building plan and highlight several interpretation’s issue

[Vaccination and celiac disease: results of a retrospective study]

Human leucocyte antigen (HLA) system plays an essential role in the human immune system activity and the expression of some specific HLA antigens could modify the immune response to vaccinations. Celiac disease is included among the diseases associated to specific HLA profiles, principally characterized by the expression of the HLA DQ2 antigen