2052 Background: Diffuse intrinsic pontine glioma (DIPG) harboring H3.3-K27M mutation is a malignant pediatric brain tumor with a >90% mortality rate within two-year of diagnosis. Current therapeutic options for DIPG are limited. Aiming to improve therapeutic outcomes, we herein report the preliminary findings of a phase I trial studying a neoantigen peptide vaccine targeting H3.3-K27M. Methods: ENACTING is an open-label, single center, two-armed phase 1 trial to assess the safety and T cell immunity of a neoantigen peptide vaccine against H3.3-K27M. Patients aged ≥ 5 years old with newly diagnosed DIPG were consented and screened. HLA-A*02+/H3.3-K27M+ patients were enrolled to a two-arm study: Arm A consists of subjects receiving open debulking surgery, and Arm B consists of subjects without surgery eligibilities who received stereotactic biopsy. All patients subsequently received conformal radiotherapy and neoantigen vaccine treatment designed to elicit both CD4+ and CD8+ T cell immune response. Vaccine was administered intramuscularly in combination with polyinosinic-polycytidylic acid-poly-L-Iysine carboxymethylcellulose (Poly-ICLC). The primary objective is to evaluate the safety (AEs graded by CTCAE v4.03) and survival outcomes. Secondary objectives include maximum tolerated dose (MTD) and immunological responses. Results: As of Jan 2023, 11 patients have been treated, with 7 in Arm A and 4 in Arm B. No grade 3-4 treatment-related adverse events have been observed, with fever (81.9%) and injection site pain (54.5%) being the most common AEs. Among 10 efficacy-assessable patients, median progression-free survival (mPFS) and median overall survival (mOS) were 11.4 months (95% CI: 5.8~14.7) and 15.4 months (95% CI: 7.53~not reached), respectively. One-year OS rate was 66.7% (95% CI: 42~100%). One patient was assessed as complete response (CR). T cell responses against neoantigen were detected and H3.3-K27M mutation-specific CD4+ and CD8+ TCR clones were validated. Conclusions: The H3.3-K27M neoantigen vaccine was well tolerated. Initial results from this ongoing study suggest that, compared with other current therapies against DIPG, H3.3-K27M peptide vaccination may provide superior patient survival outcomes. Clinical trial information: NCT04749641 . [Table: see text]
Recycling valuable metals from waste streams has become increasingly important to the mining and smelting industry in China due to resource depletion and environmental concerns. Predicated on multiple large scale metal recovery operations designed by BQE Water at active mines in the Jiangxi Province of China, this paper presents a case study demonstrating recovery of zinc and copper from the waste stream at a major gold smelter in the Shandong Province of China. One of the issues facing the smelter is the lack of a cost-effective and robust process to recover zinc from the acidic process waste stream. As such, significant amounts of zinc-containing wastewater are neutralized with lime, resulting in not only the loss of zinc metal but also the generation of large volumes of sludge. In the case study, a sulphide precipitation process is chosen to selectively recover zinc and copper from the wastewater, in the form of commercial grade metal concentrates that can be sold as regular concentrates at the going market price. In the current project phase, over 2,500 tonnes of zinc metal and 40 tonnes of copper metal can be recovered on an annual basis. This not only generates revenue to offset waste treatment costs, but also eliminates significant amounts of sludge that would otherwise require storing and further disposal if the metals are not recovered.
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