Cutting Edge: Endotoxin Tolerance in Mouse Peritoneal Macrophages Correlates with Down-Regulation of Surface Toll-Like Receptor 4 Expression1
A decrease in inflammatory cytokine production in tolerant macrophages well correlates with down-regulation of the surface TLR4 expression, which may explain one of the mechanisms for LPS tolerance.
Synergy and Cross-Tolerance Between Toll-Like Receptor (TLR) 2- and TLR4-Mediated Signaling Pathways1
- Shintaro Sato, F. Nomura, S. Akira
- Biology, MedicineJournal of Immunology
- 15 December 2000
Findings indicate that LPS-induced LPS tolerance mainly occurs through the down-regulation of surface expression of the TLR4-MD2 complex; in contrast, MALP-2-inducedLPS tolerance is due to modulation of the downstream cytoplasmic signaling pathways.
Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity
Overexpression of DAPK2, but not the kinase negative mutant, significantly induced the morphological changes characteristic of apoptosis, indicating that DAPk2 is an additional member of D AP kinase family involved in apoptotic signaling.
Iκb Kinase α Is Essential for Mature B Cell Development and Function
Results demonstrate that IKKα is critically involved in the prevention of cell death and functional development of mature B cells and transgene expression of bcl-2 could only partially rescue impaired B cell development in IKK α−/− chimeras.
IL-18-deficient mice are resistant to endotoxin-induced liver injury but highly susceptible to endotoxin shock.
It is demonstrated that IL-18 is responsible for the progression of endotoxin-induced liver injury as well as down-regulation of endot toxin-induced TNF-alpha production in P. acnes-primed mice.
Uptake of 111In-labeled fully human monoclonal antibody TSP-A18 reflects transferrin receptor expression in normal organs and tissues of mice.
The findings suggest that the difference in TfR expression between murine strains should be carefully considered when testing for the toxicity of anti-TfR antibody in mice and the uptake ofAnti-T fR antibody could reflect tissue T fR expression more accurately compared with that of transferrin-mediated imaging probe such as [67Ga]citrate.
Abstract 5586: PPMX-T003, a fully human anti-TfR1 antibody with potent efficacy against hematologic malignancies
- Lilin Zhang, F. Nomura, Yoichi Aikawa, Y. Kurosawa, K. Morishita, Yukio Sudo
- 1 July 2017
A fully human antibody against TfR1, PPMX-T003, was developed, which displayed potent anti-tumor activity in vitro and in vivo and showed potent efficacy against several blood cancer xenograft models.
Phase I Study of P-cadherin–targeted Radioimmunotherapy with 90Y-FF-21101 Monoclonal Antibody in Solid Tumors
- V. Subbiah, W. Erwin, G. Ravizzini
- Medicine, BiologyClinical Cancer Research
- 18 August 2020
The favorable safety profile and initial antitumor activity observed for 90Y-FF-21101 warrant further evaluation of this radioimmunotherapeutic (RIT) approach and provide initial clinical data supporting P-cadherin as a potential target for cancer treatment.
Anti-Cadherin 3 antibody labeled with Y-90 effectively inhibits tumor growth of non-small cell lung cancer xenograft in nude mice by radioimmunotherapy
- H. Satoh, F. Nomura, Yukio Sudo
- 1 May 2010
Phase 1 Clinical Trial of PPMX-T003, a Novel Human Monoclonal Antibody Specific for Transferrin Receptor 1, to Evaluate Its Safety, Pharmacokinetics, and Pharmacodynamics.
- Y. Ogama, Yuji Kumagai, Yukiya Yamamoto
- Medicine, BiologyClinical pharmacology in drug development
- 30 December 2022
The antibody-mediated blockade of TFR1 elicited the expected fall in blood cell levels and showed an acceptable safety profile, supporting the continuing development of PPMX-T003 as a new candidate for polycythemia vera treatment.