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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.
CBX2 suppresses interferon signaling to diminish tumor immunogenicity via a noncanonical corepressor complex.
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China.
Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti-PD1 or adoptive T cell therapies by using murine syngeneic tumor models.
View Article and Find Full Text PDFSIV monoclonal antibody administration spanning treatment interruption in macaques delays viral rebound and selects escape variants.
Proc Natl Acad Sci U S A
February 2025
U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
HIV-1 envelope broadly neutralizing antibodies represent a promising component of HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal antibodies (mAbs) in a rigorous nonhuman primate model, we tested different combinations of simian immunodeficiency virus (SIV) neutralizing mAbs in SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV mAbs targeting multiple Env epitopes spanning analytical treatment interruption (ATI) in 3 groups (n = 7 each): i) no mAb; ii) 4-mAb combination; and iii) 2-mAb combination.
View Article and Find Full Text PDFEffect of cytotoxic CD8+ T-cells secretory proteins on hypoxic pancreatic cancer cells.
PLoS One
January 2025
Cell Therapy Center, The University of Jordan, Amman, Jordan.
Background: Hypoxia in tumor cells is linked to increased drug resistance and more aggressive behavior. In pancreatic cancer, the tumor microenvironment is notably hypoxic and exhibits strong immunosuppressive properties. Given that immunotherapy is now approved for pancreatic cancer treatment, further understanding of how pancreatic tumor cell hypoxia influences T-cell cytotoxicityis essential.
View Article and Find Full Text PDFAccurate Physics-Based Prediction of Binding Affinities of RNA- and DNA-Targeting Ligands.
J Chem Inf Model
January 2025
Schrödinger Incorporated, Cambridge, Massachusetts 02142, United States.
Article Synopsis
- Predicting how well ligands bind to nucleic acids is challenging, which limits the development of small-molecule drugs for diseases like cancer and infections.
- Recent advancements in computational methods, particularly free-energy perturbation (FEP), have improved predictions for protein-ligand binding affinities, but its effectiveness for nucleic acids was unclear.
- This study found that using FEP+ software with the OPLS4 force field can accurately predict binding energies for over 100 ligands interacting with DNA/RNA, achieving predictions that closely match experimental data and could aid drug discovery.
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