Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors

Non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase inhibitors (TKIs), but is successful for only a limited amount of time; most cases relapse due to the development of drug resistance. Here we show that a vaccine against ALK induced a strong and specific immune response that both prophylactically and therapeutically impaired the growth of ALK-positive lung tumors in mouse models. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. We found that lung tumors containing ALK rearrangements induced an immunosuppressive microenvironment, regulating the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti-PD-1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune checkpoint blockade therapies might represent a powerful strategy for the treatment of ALK-driven NSCLC

Effect of Processing History and Buffer-Composition on Peanut and Hazelnut Protein Extraction Efficiency.

Abstract not availableJRC.D-Institute for Reference Materials and Measurements (Geel

Inter-laboratory Validation Study of Two Commercial Lateral Flow Devices for the Detection of Peanut Proteins in Cookies

The results of an inter-laboratory study with two commercially available lateral flow devices (dipstick tests) designed to detect peanut residues in food matrices are reported. The test samples used in this study were cookies containing peanut at seven different concentrations in the range of 0 – 30 mg peanut per kg food matrix. The test samples with sufficient and proven homogeneity were prepared in our laboratory. The analyses of the samples (5 times per level and each laboratory) were performed by 18 laboratories worldwide that submitted in total 1 260 analytical results. One laboratory was found to be an outlier for one of the test kits. In general, both test kits performed well. However, there were some false-negative results in all matrices below 21 mg peanut/kg cookie. It must be stressed that the test kits were challenged beyond their cut-off limits (5 mg/kg or more depending on the food matrix). One test kit showed less false-negative results whereas it led to some false-positives in the blank materials. The sensitivity of the dipstick tests is comparable to what can be achieved with enzyme-linked immunosorbent assays (ELISA).JRC.D.8-Food safety and qualit

Results of an Inter-laboratory Validation Study of Five Commercial ELISA Test Kits for the Determination of Peanut Proteins in Biscuits and Dark Chocolate

The results of an inter-laboratory study with five commercially available peanu ELISA test kits to detects and quantify peanut residues in two food matrices (biscuit and dark chocolate) at four different concentrations( O-10 mg peanut kg-1 matrix corresponding to about 0-2.5 mg peanut protein kg-1 matrix) are reported. In general the fice ELISA test kits evaluated could detect peanut protein in the two food matrices. In three cases, the study challenged the test kits beyond their intended use for quantification below the manufacturers' defined cut-off limits. Generally, all five ELISA test kits performed well in the concentration range 5-10 mg kg-1 rather than in the low concentrations range (2.0 to 2.5 mg kg-1). The variation in the found recoveries of peanut between the different test kits had a spread of 44-191% across all concentrations. The quantification characteristics between test kits differed significantly at the very low mg kg-1 level. Two test kits performed well even at concentrations below 5 mg kg-1 with reproducibilities ot 27-36% for biscuits and 45-57% for chocolate.JRC.D.8-Food safety and qualit

Everolimus restores gefitinib sensitivity in resistant non-small cell lung cancer cell lines

The epidermal growth factor receptor (EGFR) is a validated target for therapy in non-small cell lung cancer (NSCLC). Most patients, however, either do not benefit or develop resistance to specific inhibitors of the EGFR tyrosine kinase activity, such as gefitinib or erlotinib. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation and survival pathways and has been associated with resistance to EGFR tyrosine kinase inhibitors. In this study, we assessed the effects of combining the mTOR inhibitor everolimus (RAD001) with gefitinib on a panel of NSCLC cell lines characterized by gefitinib resistance and able to maintain S6K phosphorylation after gefitinib treatment. Everolimus plus gefitinib induced a significant decrease in the activation of MAPK and mTOR signaling pathways downstream of EGFR and resulted in a growth-inhibitory effect rather than in an enhancement of cell death. A synergistic effect was observed in those cell lines characterized by high proliferative index and low doubling time. These data suggest that treatment with everolimus and gefitinib might be of value in the treatment of selected NSCLC patients that exhibit high tumor proliferative activit