Expansion and Characterization of Human Melanoma Tumor-Infiltrating Lymphocytes (TILs)

Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution.TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×10(7) TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day "rapid expansion protocol" (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/- 1034-fold) after 14 days.TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Recycling waste plastics as hollow fiber substrates to improve the anti-wettability of supported ionic liquid membranes for CO2 separation

In this study, hydrophobic waste poly(styrene-co-butadiene)-derived polymeric hollow fiber fabricated via a dry-jet wet spinning method were used as substrates to support ionic liquid (IL) membranes via the dip-coating method. The surface properties of the substrates, such as pore size and its distribution, roughness, and wettability, were adjusted by changing the air gap distance during the spinning process. The roughness of the outer surface of the substrates decreased from 5.57 nm to 3.81 nm as the air gap increased from 0 cm to 20 cm. As a smoother surface was obtained, the wetting stability of the substrate was enhanced, thereby promoting thin supported ionic liquid membranes (SILMs) formation. The SILMs obtained were used to separate CO2 gas from N2, and the separation performance of single and binary gases and long-term stability of SILMs were evaluated. Results indicated that the use of sponge-like hollow fibers as a substrate yields a CO2 permeability of over 745.74 barrer and CO2/N2 selectivity of 17.8. Furthermore, when the transmembrane pressure was enhanced to 2.25 bar, the SILMs exhibited good membrane stability, an enhanced CO2 permeability of 1018.54 barrer, and a CO2/N2 selectivity of 20.17. This study revealed that the wetting behavior of IL is affected by the pore structure and surface roughness of the hollow fibers. Therefore, the surface property of substrates is a key point in improving the completeness and stability of SILMs in the gas separation process