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The Research Agenda for Perinatal Innovation and Digital Health Project: Human-Centered Approach to Multipartner Research Agenda Codevelopment.
JMIR Hum Factors
January 2025
Women's Health Research Institute, Vancouver, BC, Canada.
Background: Digital health innovations provide an opportunity to improve access to care, information, and quality of care during the perinatal period, a critical period of health for mothers and infants. However, research to develop perinatal digital health solutions needs to be informed by actual patient and health system needs in order to optimize implementation, adoption, and sustainability.
Objective: Our aim was to co-design a research agenda with defined research priorities that reflected health system realities and patient needs.
Results From First-in-Human Phase I Study of a Novel CD19-1XX Chimeric Antigen Receptor With Calibrated Signaling in Large B-Cell Lymphoma.
J Clin Oncol
January 2025
Center for Cell Engineering, Sloan Kettering Institute, New York, NY.
Purpose: We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3ζ and 4-1BB/CD3ζ CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities.
View Article and Find Full Text PDFDiscovery, Optimization, and Preclinical Pharmacology of EP652, a METTL3 Inhibitor with Efficacy in Liquid and Solid Tumor Models.
J Med Chem
January 2025
Epics Therapeutics SA, rue Adrienne Bolland 47, Gosselies 6041, Belgium.
METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.
View Article and Find Full Text PDFCBX2 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.
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