CDX-1140 has unique properties relative to other CD40 agonist antibodies: potent agonist activity resulting in dendritic cell and B cell activation is independent of Fc receptor interaction, contributing to more consistent, controlled immune activation; CD40 ligand
binding is not blocked, allowing potential synergistic, antigen-specific agonist activity; and the antibody promotes strong immune activation without significant adverse events in preclinical toxicology studies.
The platform combines three mRNAs coding for constitutively activated TLR4, CD40 ligand
, and CD70 that act synergistically on distinct pathways to activate dendritic cells, which play a critical role in anti-tumor immune responses.
Human B cell proliferation and Igsecretion induced by recombinant CD40 ligand
are modulated by soluble cytokines.
We measured blood levels of 10 cytokines including 6 pro-inflammatory cytokines [interleukin-1 (IL-1; gene name: IL1), interleukin-6 (IL-6; gene name: IL6), tumor necrosis factor-[alpha] (TNF-[alpha]; gene name: TNF), toll-like receptor-2 (TLR-2; gene name: TLR2), CD40 ligand
(CD40L; gene name: CD40LG), and intercellular adhesion molecule-1 (ICAM-1; gene name: ICAM1)], two procoagulant cytokines [tissue factor (F3; gene name: F3) and plasminogen activator inhibitor-1 (PAI-1; gene name: SERPINE1)], and two vasoconstrictors [endothelin-1 (ET-1; gene name: EDN1) and angiotensin converting enzyme-1 (ACE-1; gene name: ACE)].
CD68, a macrophage inflammatory marker, was increased by 2.5-fold in BDL rats (P < 0.01), and there was an evident upregulation in members of the tumour necrosis factor super family genes such as CD40 (1.7-fold, P < 0.01) and CD40 ligand
(1.9-fold, P < 0.01) in the liver of BDL rats (Figures 3(d), 3(g), and 3(h)).
The interaction between CD40 on APCs and CD40 ligand
(CD40L) on activated T cells is required for the SS onset in the NOD.H-2h4 mouse model [40, 41].
XHIGM is caused by defects in the CD40LG/TNFSF5 gene, encoding for CD40 ligand
(CD40LG) (OMIM#300386), a molecule predominantly expressed by activated CD4+ T lymphocytes .
In this study, we investigated the effect of soluble CD40 ligand
(sCD40L) and clotting activation on children and adolescents with hypercholesterolemia.
Grafe et al., "CD40 ligand
on activated platelets triggers an inflammatory reaction of endothelial cells," Nature, vol.
The more recent form of immune suppression utilized in hCXTx is costimulation blockade, primarily directed at the CD154 (CD40 ligand
) and CD40 secondary signaling pathway, to block Th2 cell help for B cell activation.
In situ expression of CD40 and CD40 ligand