Pre-treatment MoS 2 NSs Co-treatment MoS 2 NSs Cell Pre-treatment MoS 2 NSs Post treatment MoS 2 NSs Pre-treatment GO NSs Co-treatment GO NSs Cell Pre-treatment GO NSs Post treatment GO NSs The interaction of 2DM with the virus is associated with color code starting from hot red being the strongest interaction to lighter until white being the weakest interaction.
Physics' curricula of Italian Scientific High Schools in the last years have been enhanced by the introduction of Quantum Mechanics and Content and Language Integrated Learning (CLIL). Education monitoring reveals that last year's students are experiencing many issues in learning in their second language (L2) and advanced and counter-intuitive contents. Our experiment is aimed at understanding and then overcoming those problems using educational methodologies based on social aspects. Thanks to the Internet, a communicative style can be exploited where teachers could keep teaching, playing the role of semiotic mediators. Multimedia and simulations broadly available in MOOCS suggested a flipped classroom approach coping with the project of CLIL lessons. In our experience two classrooms of students were selected, starting from very similar performances and skills. The first one was taught with traditional lectures and tests; the second one, instead, attended to experimental lessons. Students could share their ideas and learning supports through a Facebook group, a blog, virtual classrooms and a website. Nevertheless, at the end of the experience an eTwinning exchange was planned, to spread the experiment towards foreign schools. The outcomes of the tests performed on the students were analysed and unexpected results were drawn. An extension to larger numbers of students, the introduction of different methodologies and the research about different topics in Physics could potentially develop this research.
BackgroundDefective DNA mismatch repair (dMMR) leads to high levels of microsatellite-instability (MSI-H) and insertions or deletions in coding regions, resulting in the generation of tumor-specific frameshift peptides (FSPs). We selected 209 shared FSPs among subjects with first- or second-line metastatic dMMR/MSI-H colorectal (CRC), gastric, and gastroesophageal junction (GEJ) cancers, to develop an off-the-shelf vaccine for the treatment of dMMR/MSI-H tumors. Selected FSPs were cloned into four proprietary Great Apes Adenoviral (GAd) and four Modified Vaccinia Ankara (MVA) vectors to generate a polyvalent viral vectored vaccine called Nous-209 [Leoni G., et al., Cancer Res. 2020]MethodsThis phase 1 first in human (FIH) study (NCT04041310) was designed to evaluate safety and tolerability of two dose levels (one log difference for both GAd and MVA) of Nous-209 genetic polyvalent vaccine in combination with the programmed death receptor-1 (PD-1)-blocking antibody pembrolizumab, to assess immunogenicity of the combination and to detect preliminary evidence of anti-tumor activity. Nous-209 is administered intramuscularly, concomitantly with pembrolizumab (doses and schedule per approved label): one prime (GAd-209-FSP) at the 2nd pembrolizumab infusion and three booster (MVA-209-FSP) injections at subsequent infusions each 3 weeks apart. The study is composed of two sequential cohorts: dose escalation and dose expansionResultsTwelve evaluable subjects with first- or second-line metastatic dMMR/MSI-H cancers were evaluated as of May 28, 2021. Three subjects enrolled in dose level 1 (2 CRC and 1 GEJ cancer) demonstrated durable confirmed partial responses (PRs). In dose level 2 (6 CRC and 3 gastric cancers), 4 subjects had PRs, 2 had stable disease (SD) and 3 had progressive disease (PD). The median follow-up for subjects in dose level 1 is 17.9 months (range 15.3–20 months), and 8 months (range 3.8–12.5 months) for subjects in dose level 2 as of the above cut-off date. No dose limiting toxicities (DLTs) were observed, and the treatment combination was determined to be safe and tolerable. Vaccine immunogenicity was demonstrated by ex-vivo interferon-gamma ELISpot assay in 67% of subjects in dose level 1, and 100% of patients with evaluable samples in dose level 2ConclusionsThe combination of the Nous-209 genetic polyvalent cancer vaccine and pembrolizumab has been demonstrated to be safe, immunogenic, and continues to show early signs of clinical efficacy, which may be attributed to the vaccine contributionReferenceLeoni G, et al. A genetic vaccine encoding shared cancer neoantigens to treat tumors with microsatellite instability. Cancer Res 2020 July 20;80(18):3972–3982.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center, IRB number 2019–0651_MOD001. The study was approved by Feinstein Institute for Medical Research Northwell Health, IRB number 19–1086. The study was approved by WCG The Trusted Partner in Ethical Review, IRB number 20200155. The study was approved by Johns Hopkins Medicine, IRB number IRB00220323/CIR00053809. The study was approved by City of Hope, IRB number 19277/176947. The study was approved by Advarra Advancing Better Research. The study was approved by Dana-Faber Cancer Institute. The study was approved by Weill Cornell IRB. The study was approved by Roswell Park IRB.
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