Phase I, First in Human, Open Label Study to Evaluate Safety and Tolerability of TRX103 Cells in Subjects With Hematological Malignancies Undergoing HLA-mismatched Related or Unrelated Hematopoietic Stem Cell Transplantation (HSCT)

The purpose of this Phase 1, first in human open-label study is to assess the safety and tolerability of TRX-103 in patients with hematological malignancies undergoing HLA-mismatched related or unrelated hematopoietic stem cell transplantation (HSCT). It is anticipated that up to 36 Subjects will be enrolled during a 18-24 month enrollment period. TRX-103 will be infused one time post HSCT.

Start Date08 Apr 2024

Sponsor / Collaborator

Tr1x, Inc.

100 Clinical Results associated with p75NTR x IL-10R

100 Translational Medicine associated with p75NTR x IL-10R

0 Patents (Medical) associated with p75NTR x IL-10R

Literatures (Medical) associated with p75NTR x IL-10R

01 Mar 2022·The FASEB JournalQ2 · BIOLOGY

proBDNF/p75NTR promotes rheumatoid arthritis and inflammatory response by activating proinflammatory cytokines

Q2 · BIOLOGY

Article

Author: Li, De‐Dong ; Han, Chen‐Yang ; Zhang, Xiao‐Yang ; Wang, Shuo ; Zhang, Xiang‐Lian ; Yang, Chun‐Rui ; Meng, Fan‐Jie ; Zhou, Fiona‐H. ; Yu, Miao ; Sun, Wei‐Zong ; Ding, Hong‐Jun ; Zhou, Xin‐Fu ; Meng, Bin ; Liang, Rui

P75 pan-neurotrophin receptor (p75NTR) is an important receptor for the role of neurotrophins in survival and death of neurons during development and after nerve injury. Our previous research found that the precursor of brain-derived neurotrophic factor (proBDNF) regulates pain as an inflammatory mediator. The current understanding of the role of proBDNF/p75NTR signaling pathway in inflammatory arthritis pain and rheumatoid arthritis (RA) is unclear. We recruited 20 RA patients, 20 healthy donors (HDs), and 10 osteoarthritis (OA) patients. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of proBDNF and p75NTR in synovial membrane were performed and evaluated. We next examined the mRNA and protein expression of proBDNF/p75NTR signaling pathway in peripheral blood mononuclear cells (PBMCs) and synovial tissue. ELISA and flow cytometry were assessed between the blood of RA patients and HD. To induce RA, collagen-induced arthritis (CIA) were induced in mice. We found over-synovitis of RA synovial membrane compared to OA controls in histologic sections. P75NTR and sortilin mRNA, and proBDNF protein level were significantly increased in PBMCs of RA patients compared with the HD. Consistently, ELISA showed that p75NTR, sortilin, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels in the serum of RA patients were increased compared with HD and p75NTR, sortilin were positively correlated with Disease Activity Score in 28 joints (DAS28). In addition, using flow cytometry we showed that the increased levels of proBDNF and p75NTR characterized in CD4⁺ and CD8⁺ T cells of RA patients were subsequently reversed with methotrexate (MTX) treatment. Furthermore, we found pathological changes, inflammatory pain, upregulation of the mRNA and protein expression of proBDNF/p75NTR signaling pathway, and upregulation of inflammatory cytokines in spinal cord using a well-established CIA mouse model. We showed intravenous treatment of recombinant p75ECD-Fc that biologically blocked all inflammatory responses and relieved inflammatory pain of animals with CIA. Our findings showed the involvement of proBDNF/p75NTR pathway in the RA inflammatory response and how blocking it with p75ECD-Fc may be a promising therapeutic treatment for RA.

01 Apr 2019·European review for medical and pharmacological sciences

IL-10 inhibits apoptosis in brain tissue around the hematoma after ICH by inhibiting proNGF.

Article

Author: Wang, H-H ; Pu, Z-X ; Song, L ; Xu, L-F

OBJECTIVETo explore the roles of interleukin-10 (IL-10), proNGF and p75NTR in apoptosis of brain tissues induced by intracerebral hemorrhage (ICH).PATIENTS AND METHODSAccording to the time of sample collection after ICH, brain tissue samples were divided into < 6 h group, 6-24 h group (including 24 h), 24-72 h group (including 72 h) and > 72 h group. Meanwhile, 10 tissues that dropped from the beginning at the cortical stoma (distal part of the hematoma) were harvested as controls. AI in brain tissues around the hematoma after ICH was calculated based on TUNEL staining. Expression levels of IL-10, proNGF and p75NTR in brain tissues were determined by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Protein expressions of Bcl-2 and Bax were detected by Western blot. Rat cortical astrocytes were harvested and cultured in vitro. After transfection of IL-10 overexpression plasmid, expression levels of IL-10, proNGF and p75NTR were detected by Western blot.RESULTSAI increased in 6-24 h group, 24-72 h group and > 72 h group compared with < 6 h group and control group, which achieved the peak at 24-72 h. However, no significant difference in AI was observed between < 6 h group and control group. With the prolongation of ICH, IL-10 level gradually decreased and achieved the lowest level at 24-72 h. After 72 h, IL-10 level began to increase. Additionally, mRNA and protein levels of proNGF and p75NTR started to upregulate within 6 h of ICH, achieveing the peak at 24-72 h. Bcl-2 level gradually decreased after 6 h of ICH, while Bax level increased. We did not found significant difference in mRNA and protein levels of IL-10 in brain tissues around hematoma between < 6 h group and control group. With the prolongation of ICH, IL-10 level gradually decreased and achieved the lowest level at 24-72 h. After 72 h, IL-10 level began to increase. Transfection with IL-10 overexpression plasmid in rat astrocytes markedly downregulated protein levels of proNGF and p75NTR compared with those of controls.CONCLUSIONSIL-10 expression is downregulated in brain tissues around the hematoma after ICH. IL-10 alleviates inflammation and apoptosis by inhibiting levels of proNGF, p75NTR and Bax/Bcl-2, thus protecting brain tissue after ICH.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis