Ask about this productRelated genes to: TL1A antibody
- Gene:
- TNFSF15 NIH gene
- Name:
- TNF superfamily member 15
- Previous symbol:
- -
- Synonyms:
- TL1, VEGI, TL1A, VEGI192A, MGC129934, MGC129935
- Chromosome:
- 9q32
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-04
- Date modifiied:
- 2017-03-02
Related products to: TL1A antibody
Related articles to: TL1A antibody
- Nonproliferative diabetic retinopathy (NPDR) is a serious and vision-threatening manifestation of diabetic eye disease. Most patients with diabetic eye disease have NPDR. Intravitreal vascular endothelial growth factor (VEGF)-neutralizing agents are able to suppress increased vascular leakage caused by poor glycemic control and are fundamental in controlling progression to vision loss. However, despite the efficacy of such treatments, the invasive nature and short interval between injections have not yielded widespread adoption in patients with NPDR. Here, we describe the effect of an orally available medication, danegaptide, in regulating retinal vascular permeability in preclinical animal models of disease and report safety and early efficacy data from an early-stage phase 1b clinical trial in patients with NPDR and mild center-involved macular edema. As an orally available gap junction modifier, danegaptide improved inner blood-retina barrier (iBRB) function through a direct connexin-43 mechanism and by working as a functional antagonist of VEGF in human retinal microvascular endothelial cells. Bulk RNA sequencing showed that danegaptide attenuated the VEGF-induced suppression of , an endogenous antagonist of VEGF activity in human retinal microvascular endothelial cells. In addition, targeted suppression of TNFSF15 using small interfering RNA or inhibition of its activity using a neutralizing antibody prevented VEGF-induced permeability in vitro and neovascular lesion development in vivo. No serious adverse events related to oral danegaptide were found in an early-stage phase 1b clinical trial in 24 patients with NPDR and mild center-involved macular edema. These findings support larger clinical trials to test efficacy. - Source: PubMed
Publication date: 2026/09/23
Hudson NataliePorkoláb GergőO'Callaghan JeffreyHanley NicoleBaccouche BasmaVarró MárkMouritzen UlrikLind Benedikte El-BandakAdamson PeterCampbell Matthew - Small cell lung cancer (SCLC) is an aggressive malignancy that responds poorly to immune checkpoint inhibitor (ICI) therapy, due to its immunosuppressive tumor microenvironment. Here, we analyse preclinical mouse tumor models and patient-derived SCLC samples and identify Exportin 1 (XPO1) as a regulator of immune suppression in SCLC. Mechanistically, XPO1 drives the nuclear export of TRIM21, enabling TRIM21-dependent proteasomal degradation of IRF3 and repressing the immunostimulatory cytokine TNFSF15. Loss of TNFSF15 promotes TREM2 macrophage polarization, which subsequently attenuates macrophage-dependent IFN-γ-STAT1 signaling and MHC class I expression in tumor cells. Pharmacological or genetic XPO1 blockade restores TNFSF15, constrains TREM2 macrophage differentiation, reactivates antigen presentation, and enhances anti-PD-1 efficacy in preclinical mouse models. Thus, our findings link XPO1-dependent nuclear export to TREM2+ macrophage polarization and support evaluation of XPO1 inhibition in combination with ICIs in SCLC. - Source: PubMed
Publication date: 2026/08/22
Du QingwuQin TingtingWang JingyaJiang YantaoXu QiLi XueyangLiu HuiyanYu JunjieLu YiTong LuyaoSun TaoChen PengJiang RichengHuang Dingzhi - - Source: PubMed
Publication date: 2026/09/11
Choi Jeong-GyuGong Eun JeongBang Chang SeokLee Jae Jun - Tumor necrosis factor-like ligand 1A (TL1A), encoded by TNFSF15, signals through death receptor 3 on effector T cells, innate lymphoid cells, and intestinal myofibroblasts, driving both chronic intestinal inflammation and tissue fibrosis. In this narrative review, we provide a contemporary appraisal of TL1A-directed therapeutics in inflammatory bowel disease based on electronic searches through May 2026. Three anti-TL1A monoclonal antibodies (tulisokibart, afimkibart, and duvakitug) have advanced to phase 3 trials across multiple global programs, with phase 2 clinical remission rates of 26%-48% in ulcerative colitis (placebo-adjusted differences 15-26 percentage points) and endoscopic response rates of 26%-48% in Crohn's disease, alongside favorable safety profiles. Mucosal transcriptomic and serum proteomic analyses from phase 2 trials, including DDW 2026 readouts from ARTEMIS-UC and TUSCANY-2, provide the first human-tissue confirmation of class antifibrotic activity through the suppression of Th17, myeloid, and extracellular matrix pathways. TNFSF15 risk-variant companion diagnostics are advancing, although their incremental utility remains modest and will be definitively tested in phase 3. The pipeline has expanded to at least 19 development programs, including extended half-life antibodies (XmAb942, SPY002, and BCD-261), bispecifics combining TL1A with IL-23 or α4β7 (RO7837195, XmAb412, LQ080, and ALX001), a first-in-class oral anti-TL1A nanobody, and a first-in-class DR3 receptor antagonist (SL-325). We discuss therapeutic positioning and timing, the opportunity in acute severe UC, and the unusual standing of IBD as the lead indication for this mechanism class. Phase 3 results anticipated in 2026-2027 will be particularly informative for fibrostenotic phenotypes and biologic-refractory patients. - Source: PubMed
Publication date: 2026/08/27
Quraishi Mohammed NabilJairath VipulAl-Bawardy Badr - TNF-like cytokine 1A (TL1A) and its receptor DR3 form a key regulatory axis within mucosal immunity, integrating signals that promote Th1/Th17 responses, modulate innate lymphoid cells, and influence epithelial repair. Beyond inflammation, TL1A directly activates intestinal fibroblasts and contributes to extracellular matrix deposition, positioning the TL1A-DR3 pathway as a central driver of both chronic inflammation and fibrosis in inflammatory bowel disease (IBD). Genetic variants in TNFSF15, which encodes TL1A, further support a causal role, linking increased TL1A expression with susceptibility to Crohn's disease, ulcerative colitis, and fibrostenotic complications. Recent clinical trials of TL1A-neutralizing antibodies, including afimkibart, tulisokibart, and duvakitug, have demonstrated encouraging efficacy and safety in moderate-to-severe IBD, with emerging biomarker strategies suggesting potential for personalized treatment. Collectively, current evidence highlights TL1A blockade as a promising dual-pathway therapeutic approach targeting inflammation and fibrotic remodeling, with ongoing studies expected to define its long-term impact on disease modification. - Source: PubMed
Publication date: 2026/08/21
Tsuruta KozoYoshioka ShinichiroTakedatsu Hidetoshi