Devon Taylor

AstraZeneca | AZ · Immunoncology

This study is aimed to investigate the effect of ATR inhibitor (ATRi) ceralasertib on tumor microenvironment (TME). Ceralasertib has demonstrated encouraging clinical benefits in patients with non-small cell lung cancer who were resistant to PD1/PDL1 treatment. Using different pre-clinical mouse tumor models, we found that antitumor effect of ceral...

The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8⁺ T-cell depende...

Background Ceralasertib is a specific ATR inhibitor (ATRi) that hinders the DNA damage response in tumor cells, making them more susceptible to death in situations of high replication stress. Ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed o...

Ferroptosis is a distinct form of cell death driven by the accumulation of peroxidized lipids. Characterized by alterations in redox lipid metabolism, ferroptosis has been implicated in a variety of cellular processes, including cancer. Induction of ferroptosis is considered a novel way to kill tumor cells, especially cells resistant to radiation a...

Background Although checkpoint inhibition has improved the treatment of metastatic non-small cell lung cancer (NSCLC), up to 65% of patients progress after initial response to PD-1/PD-L1 targeting strategies, suggesting additional immune therapies are required to further improve patient outcome.¹ TIGIT is a receptor of the Ig superfamily, which pla...

Background The performance of the Roche Elecsys® Anti-SARS-CoV-2, Abbott Architect SARS-CoV-2 IgM and IgG, Euroimmun SARS-CoV-2 IgA, Euroimmun SARS-CoV-2 IgG ELISA, and Trillium IgG/IgM rapid assays was evaluated in Jamaica. Methods Diagnostic sensitivities of the assays were assessed by testing serum samples from SARS-CoV-2 PCR-confirmed persons...

The performance of the Roche Elecsys ® Anti-SARS-CoV-2, Abbott Architect SARS-CoV-2 IgG, Euroimmun SARS-CoV-2 IgA, Euroimmun SARS-CoV-2 IgG ELISA, and Trillium IgG/IgM rapid assays was evaluated in Jamaica, the largest country of the English-speaking Caribbean. Diagnostic sensitivities of the assays were assessed by testing serum samples from SARS-...

Systemic lupus erythematosus (SLE) impacts multiple organ systems, although the causes of many individual SLE pathologies are poorly understood. This study was designed to elucidate organ-specific inflammation by identifying proteins that correlate with SLE organ involvement and to evaluate established biomarkers of disease activity across a divers...

Systemic sclerosis (SSc) is a debilitating inflammatory and fibrotic disease that affects the skin and internal organs. Although the pathophysiology of SSc remains poorly characterized, mononuclear cells, mainly macrophages and T cells, have been implicated in inflammation and fibrosis. Inducible costimulator (ICOS), which is expressed on a subset...

MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (TFH) cells. Effects of MEDI-570 were evaluated in an enhanced pre-postnatal development toxicity (ePPND) study in cynomolgus monkeys. Administration to pregnant monkeys did cause any abortifaci...

IL-21 and IFNa are increased in several autoimmune syndromes including Rheumatoid Arthritis (RA). These cytokines have pleiotropic actions on cell types of lymphoid and non-lymphoid origin and both have been reported to induce plasma cell differentiation. In a cohort of RA patients (n=42), we tested if a correlation exists between IL-21 and type I...

The inducible co-stimulatory molecule inducible T-cell co-stimulator (ICOS) is expressed during activation of T helper cells and prominently on T follicular helper (TFH) cells. ICOS regulates TFH cells required for follicular and extrafollicular T cell-dependent B-cell responses. Increased ICOS expression on T cells from patients with autoimmune di...

It is well established that Toll-like receptors (TLRs) play a critical role in the generation of innate immune responses and thereby also play an important, indirect role in the initiation of subsequent adaptive T cell responses. However, T cells also express certain TLRs, and we have focused on the physiological importance of direct TLR signaling...

During acute lymphocytic choriomeningitis virus (LCMV) infection, CD8 T cells rapidly expand and differentiate into effectors that are required for viral clearance. The accumulation of activated T cells is greatly reduced in mice lacking the adaptor molecule MyD88. Although MyD88 has generally been considered to indirectly regulate adaptive immune...

Resistance to Toxoplasma gondii depends on dendritic cells to recognize this pathogen and secrete IL-12, in turn promoting IFN-γ production from responding T cells. The adaptor protein, myeloid differentiation primary-response gene 88 (MyD88), is important for most Toll-like receptor (TLR) signaling, as well as IL-1R/IL-18R signals. There is consid...

Toll-like receptors (TLR) play an integral role in bridging the innate and adaptive response. The stimulation of TLRs on antigen presenting cells promotes their maturation through the upregulation of MHC class II molecules, costimulatory ligands, the release of pro-inflammatory cytokines. Emerging data support the presence of TLR2, 3, 5, 8 and 9 on...

One of the greatest barriers against harnessing the potential of CD4+ CD25+ Tregs as a cellular immunotherapy is their hypoproliferative phenotype. We have previously shown that the hypoproliferative response of Tregs to IL-2 is associated with defective downstream PI3K signaling. Here, we demonstrate that targeted deletion of the lipid phosphatase...

The transcription factor STAT5 is one of several signaling mediators activated via common gamma-chain cytokine receptors. As such, it plays an important role in lymphocyte survival and proliferation during normal homeostasis as well as under lymphopenic conditions. Transgenic mice expressing a constitutively activated form of STAT5b have been shown...

Mice transgenic for the R4A-Cmu heavy chain of an anti-dsDNA antibody, maintain tolerance by anergy and deletion. In C57BL/6 mice overexpressing CD19, a molecule, which lowers the threshold for B cell activation, elevated levels of serum autoantibodies have been observed. In the present study, we wished to determine whether CD19 overexpression coul...

The induction and maintenance of immune tolerance to transplanted tissues constitute an active process involving multiple mechanisms that work cooperatively to prevent graft rejection. These mechanisms are similar to inherent tolerance toward self antigens and have a requirement for active immunoregulation, largely T cell mediated, that promotes sp...

The different threshold of activation for memory T cells compared to that of naïve T cells makes them resistant to immunomodulation, thus representing a barrier to tolerance. Recently it has been demonstrated that homeostatic proliferation and heterologous immunity represent two naturally occurring and distinct processes that can generate memory T...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the production of anti-nuclear antibodies. The etiology of SLE is unknown, although several viruses including the Epstein-Barr virus (EBV) have been implicated. An increase in the frequency of EBV infection has been observed in SLE patients relative to normal indiv...

One mechanism by which anti-double stranded (ds) DNA B cells are regulated is anergy. Multiple phenotypes have been attributed to anergic B cells in various transgenic models. Differences in the nature of the antigen and in the avidity of antigen-antibody interactions may account for these variations in phenotype. In the present study we describe a...