Do CARs need a driver's license? Adoptive cell therapy with chimeric antigen receptor-redirected T cells caused serious adverse events

Adoptive transfer of genetically retargeted T cells provides promise in the therapy of malignant diseases; two severe adverse events, however, due to "on-targeted" activation of modified T cells occurred in recent trials. We here discuss the challenge to balance targeted anti-tumor responses whilst avoiding destruction of healthy tissues and the need of continued and carefully designed pre-clinical and clinical evaluations

The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor

The effect of the dietary flavonoid galangin on the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), the activity of cytochrome P 450 1A1 (CYP1A1), and the expression of CYP1A1 in MCF-7 human breast carcinoma cells was investigated. Galangin inhibited the catabolic breakdown of DMBA, as measured by thin-layer chromatography, in a dose-dependent manner. Galangin also inhibited the formation of DMBA-DNA adducts, and prevented DMBA-induced inhibition of cell growth. Galangin caused a potent, dose-dependent inhibition of CYP1A1 activity, as measured by ethoxyresorufin-O-deethylase activity, in intact cells and in microsomes isolated from DMBA-treated cells. Analysis of the inhibition kinetics by double-reciprocal plot demonstrated that galangin inhibited CYP1A1 activity in a non-competitive manner. Galangin caused an increase in the level of CYP1A1 mRNA, indicating that it may be an agonist of the aryl hydrocarbon receptor, but it inhibited the induction of CYP1A1 mRNA by DMBA or by 2,3,5,7-tetrachlorodibenzo-p-dioxin (TCDD). Galangin also inhibited the DMBA- or TCDD-induced transcription of a reporter vector containing the CYP1A1 promoter. Thus, galangin is a potent inhibitor of DMBA metabolism and an agonist/antagonist of the AhR, and may prove to be an effective chemopreventive agent. © 1999 Cancer Research Campaig

Parametrische, nichtparametrische, robuste und adaptive Tests - Modelle, Hypothesen und Effizienz am Beispiel des unverbundenen Zweistichproben-Problems

SIGLETIB: RN 6494 (1986,1) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman