engineered authentic cells / Bayer - LARVOL DELTA

Influence of a Th17-Inducing Cytokine Milieu on Phenotypical and Functional Properties of Regulatory T Cells in Chronic Inflammatory Arthritis. (PubMed, Int J Mol Sci) - "To clarify this conundrum, in vitro stimulation of isolated Treg cells with Th17-inducing cytokines (IL-1β, IL-6, IL-23, TGFβ), recombinant IL-17, or the anti-IL-17A antibody secukinumab was performed, demonstrating that cell culture conditions polarizing towards Th17, but not IL-17 itself, impair the suppressive function of Treg cells, accompanied by diminished FOXP3 mRNA expression due to hypermethylation of the FOXP3 promotor and TSDR. This potential causal relationship between Th17 inflammation and impaired Treg cell function requires attention regarding the development of immunomodulatory therapies."

Journal • Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • FOXP3 • IL17A • IL1B • IL23A • IL6 • TGFB1

Identification of synergistic drug combinations including MEK inhibitor and agents modulating the tumor microenvironment in an electroporation-induced pancreatic cancer model (CIMT 2024) - "Apart from the direct cytostatic impact of MEKi on the Kras-transformed tumor cells, the mechanism of action of this synergistic drug combination involves enhancement of the anti-tumor T-cell response, suppression of CD4+ Treg cells, and reduction of MDSCs and M2-type macrophages in favor of M1-type pro-inflammatory macrophages. In contrast to the aforementioned regimen, the complementary action of these drugs involves modulation of the TME by regorafenib. While the clinical translation of the MEKi/CD40 Ab regimen is hampered by toxicity issues encountered with agonist anti- CD40 Ab, the synergy as observed in the MEKi/regorafenib regiment provides a tangible path towards clinical testing."

Biomarker • IO biomarker • Preclinical • Tumor microenvironment • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CDKN2A • KRAS • SMAD4 • TP53

Regorafenib enhances anti-PD1 immunotherapy efficacy in murine colorectal cancers and their combination prevents tumor regrowth. (PubMed, J Exp Clin Cancer Res) - "This study highlights the synergistic immunomodulatory effects of REG and aPD1 combination therapy in mediating a sustained inhibition of colon cancer regrowth, strongly warranting clinical evaluation in CRC, including MSS tumors."

IO biomarker • Journal • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • IFNG • MRI