Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909

T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials. To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated. No clinical responses were observed. Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination. In contrast, a significant decline in vaccine-specific CD8+ T cells was observed. An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased. Taken into considerations that multiple clinical trials with identical antigens but different adjuvants induced vaccine-specific T cell responses, our data caution that a vaccination with leukemia-associated antigens can be detrimental when combined with MontanideISA51 and CpG7909. Reflecting the time-consuming efforts of clinical trials and the fact that 1/3 of ongoing peptide vaccination trails use CpG and/or Montanide, our data need to be taken into consideration

Perspectives for regulating 10 nm particle number emissions based on novel measurement methodologies

Concerns regarding noxious emissions from internal combustion engines have increased over the years. There is a strong need to understand the nature of sub-23 nm particles and to develop measurement techniques to evaluate the feasibility of new regulations for particle number emissions in the sub-23 nm region (down to at least 10 nm). This paper presents the results of three EU-funded projects (DownToTen, PEMs4Nano and SUREAL-23) which supported the understanding, measurement and regulation of particle emissions below 23 nm and have successfully developed sub-23 nm particle measurement devices, specifically laboratory systems and mobile devices for RDE tests. The new technology was validated in chassis dyno tests and on the real road. The results show that sub-23 nm particles are mainly generated at the engine start and during acceleration phases. The innovations show that the technology is mature and robust enough to serve as a basis for regulating sub-23 nm particles.The DownToTen project has received funding from the European Union's Horizon 2020 research and innovation programme under agreement No 724085. The PEMs4Nano project has received funding from the European Union's Horizon 2020 research and innovation programme under agreement No 724145. The SUREAL-23 project has received funding from the European Union's Horizon 2020 research and innovation programme under agreement No 724136