Flowjo 7.6.5 free download trial#

As any polypeptide-based antigen can be encoded as RNA 3, 4, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency.

Flowjo 7.6.5 free download trial#

A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated 2. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands.

However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Our work shows that bacteria use stress responses to detect and respond to competition in a manner important for major phenotypes, including biofilm formation, virulence, and antibiotic tolerance.Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses 1. Moreover, inactivation of the type VI secretion system (T6SS) of a competitor annuls the responses to competition, indicating that T6SS-derived cell damage activates these stress response systems. We further show that these responses arise via activation of major stress responses, providing direct support for the competition sensing hypothesis. We validate that these regulatory changes result in the predicted phenotypic changes in biofilm, mammalian cell invasion, and antibiotic tolerance.

This screening reveals the presence of competing strains drives up the expression of genes associated with biofilm matrix production (CsgD pathway), epithelial invasion (SPI1 invasion system), and, finally, chemical efflux and antibiotic tolerance (TolC efflux pump and AadA aminoglycoside 3-adenyltransferase). Here, we solve this problem by using differential fluorescence induction to screen the Salmonella Typhimurium genome for loci that respond, at the single-cell level, to life in biofilms with competing strains of S. The competition sensing hypothesis states that bacterial stress response systems can serve to detect ecological competition, but studying regulatory responses in diverse communities is challenging. Bacteria use complex regulatory networks to cope with stress, but the function of these networks in natural habitats is poorly understood.