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Oncolytic reprogramming of tumor microenvironment shapes CD4 T-cell memory via the IL6ra-Bcl6 axis for targeted control of glioblastoma.
Nat Commun
January 2025
Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Oncolytic viruses (OVs) emerge as a promising cancer immunotherapy. However, the temporal impact on tumor cells and the tumor microenvironment, and the nature of anti-tumor immunity post-therapy remain largely unclear. Here we report that CD4 T cells are required for durable tumor control in syngeneic murine models of glioblastoma multiforme after treatment with an oncolytic herpes simplex virus (oHSV) engineered to express IL-12.
View Article and Find Full Text PDFSafety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study.
RMD Open
January 2025
Department of Internal Medicine and Rheumatology, Schlosspark Klinik, University Medicine Berlin, Berlin, Germany.
Objectives: DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.
Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol.
Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS: Nine-Year Data From the OPERA Studies Open-Label Extension.
Neurology
February 2025
Department of Neurology and Center of Clinical Neuroscience, First Medical Faculty, General University Hospital and Charles University, Prague, Czech Republic.
Background And Objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).
Methods: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies.
The dynamics of CD4+ T cell proliferation and regulation.
J Biol Dyn
December 2025
School of Mathematics and Statistics, Donghua University, Shanghai, People's Republic of China.
We use mathematical modeling to study the proliferation dynamics of CD4+ T cells within an immune response. This proliferation is driven by the autocrine reaction of helper T cells and interleukin-2 (IL-2), and regulated by natural regulatory T cells (nTregs). Previous studies suggested that a fratricidal mechanism is necessary to eliminate helper T cells post-infection.
View Article and Find Full Text PDFAdaptive Immunity Determines the Cancer Treatment Outcome of Oncolytic Virus and Anti-PD-1.
Bull Math Biol
January 2025
Department of Mathematics, University of Manitoba, 340 UMSU University Centre, Winnipeg, MB, R3T 2N2, Canada.
The immune checkpoint inhibitor, anti-programmed death protein-1 (anti-PD-1), enhances adaptive immunity to kill tumor cells, and the oncolytic virus (OV) triggers innate immunity to clear the infected tumor cells. We create a mathematical model to investigate how the interaction between adaptive and innate immunities under OV and anti-PD-1 affects tumor reduction. For different immunity strength, we create the corresponding virtual baseline patients and cohort patients to decipher the major factors determining the treatment outcome.
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