Influence of thiophanate-methyl and methyl-benzimidazole-2yl-carbamate on mycotoxin producing Fusarium spp.

Bei der Untersuchung des Einflusses von Thiophanat-Methyl und Methyl-Benzimidazol-2yl-Carbamat auf mykotoxinbildende Arten von Fusarium spp. konnte beobachtet werden, dass Thiophanat-Methyl einen deutlich stärkeren Einfluss auf die Biosynthese der Mykotoxine als auf das Wachstum der Pilze aufwies und die Respiration von Fusarium spp. im Flüssigmedium unabhängig vom Myzelwachstum gehemmt wurde. Die Ergebnisse weisen somit auf einen zusätzlichen Wirkungsmechanismus von Thiophanat-Methyl in Fusarium spp. hin.Investigations into the effect of thiophanat-methyl and methyl-benzimidazole-2yl-carbamat on mycotoxinproducing species of Fusarium spp. showed that the influence on the biosynthesis of mycotoxins was more distinct than on the growth of the fungi. Moreover Fusarium spp. showed a reduced respiration at certain levels of TM that was not associated with an inhibited growth. The data indicate that there may be a mechanism of thiophanat-methyl by which the mycotoxinformation of Fusarium spp. could be inhibited independant from the growth of the mycelium

Einfluss von Thiophanat-Methyl und Methyl-Benzimidazol-2yl-Carbamat auf mykotoxinbildende Fusarium spp.

ZusammenfassungBei der Untersuchung des Einflusses von Thiophanat-Methyl und Methyl-Benzimidazol-2yl-Carbamat auf mykotoxinbildende Arten von Fusarium spp. konnte beobachtet werden, dass Thiophanat-Methyl einen deutlich stärkeren Einfluss auf die Biosynthese der Mykotoxine als auf das Wachstum der Pilze aufwies und die Respiration von Fusarium spp. im Flüssigmedium unabhängig vom Myzelwachstum gehemmt wurde. Die Ergebnisse weisen somit auf einen zusätzlichen Wirkungsmechanismus von Thiophanat-Methyl in Fusarium spp. hin. AbstractInvestigations into the effect of thiophanat-methyl and methyl-benzimidazole-2yl-carbamat on mycotoxinproducing species of Fusarium spp. showed that the influence on the biosynthesis of mycotoxins was more distinct than on the growth of the fungi. Moreover Fusarium spp. showed a reduced respiration at certain levels of TM that was not associated with an inhibited growth. The data indicate that there may be a mechanism of thiophanat-methyl by which the mycotoxinformation of Fusarium spp. could be inhibited independant from the growth of the mycelium.Keywords: Fusarium spp., thiophanat-methyl, carbendazim, mycotoxinproductio

A novel anti-B7-H3 chimeric antigen receptor from a single-chain antibody library for immunotherapy of solid cancers

B7-H3 (CD276) has emerged as a target for cancer immunotherapy by virtue of consistent expression in many malignancies, relative absence from healthy tissues, and an emerging role as a driver of tumor immune inhibition. Recent studies have reported B7-H3 to be a suitable target for chimeric antigen receptor-modified T cell (CAR-T) therapy using CARs constructed from established anti-B7-H3 antibodies converted into single-chain Fv format (scFv). We constructed and screened binders in an scFv library to generate a new anti-B7-H3 CAR-T with favorable properties. This allowed access to numerous specificities ready formatted for CAR evaluation. Selected anti-human B7-H3 scFvs were readily cloned into CAR-T and evaluated for anti-tumor reactivity in cytotoxicity, cytokine, and proliferation assays. Two binders with divergent complementarity determining regions were found to show optimal antigen-specific cytotoxicity and cytokine secretion. One binder in second-generation CD28-CD3ζ CAR format induced sustained in vitro proliferation on repeat antigen challenge. The lead candidate CAR-T also demonstrated in vivo activity in a resistant neuroblastoma model. An empirical approach to B7-H3 CAR-T discovery through screening of novel scFv sequences in CAR-T format has led to the identification of a new construct with sustained proliferative capacity warranting further evaluation

Functional avidity of anti-B7H3 CAR-T constructs predicts antigen density thresholds for triggering effector function

Chimeric Antigen receptor T cell (CAR-T) treatments for solid cancers have been compromised by limited expansion and survival in the tumor microenvironment following interaction with antigen-expressing target cells. Using B7H3 as a model antigen with broad clinical applicability, we evaluate the relationship between the antibody/antigen affinity of three clinical candidate binders and the three following characteristics: cellular avidity, duration of sustained cytotoxicity in tumoroid re-stimulation assays, and in vivo anti-tumoral responses. Next, BEHAV3D video microscopy is used to assess CAR-T cell interaction with tumor cells at single cell resolution. These data are consistent with a threshold avidity of CAR-T / tumor cell interaction and target cell B7H3 expression level, where enhanced functionality is characterized by longer cumulative CD8+ CAR-T / tumor target interaction times, CAR-T cell expansion and sustained tumor control. Lower checkpoint receptor expression does not correlate with enhanced anti-tumor function. These results provide further insights into design of anti-B7H3 CAR-T cells for antigen-dim cell targeting, and avoidance of antigen-dim tumor relapse