FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2316508538> ?p ?o ?g. }

• W2316508538 endingPage "1158" @default.
• W2316508538 startingPage "1158" @default.
• W2316508538 abstract "Purpose: Current induction agents are well known for their broad immune modulating activity. TOL101 is a novel monoclonal antibody that is specific for the ab TCR. It is currently in Phase 2 testing in the United States. This interim analysis describes the kinetics of peripheral blood leukocytes in 20 subjects undergoing an initial kidney transplant from a living donor. Methods: Six cohorts (ranging from 0.28, 1.4, 7, 14, 28, and 42 mg) received TOL101 daily for atleast 6 doses at successively higher dose levels. Maintenance therapy was tacrolimus, mycophenolate, and steroids. Multi-parametric flow cytometry was performed on blood samples, and the presence of pro-inflammatory cytokines IFNg, TNF, IL-1b, IL-6, and IL-10 was determined by multiplex ELISA (Luminex). Pharmacokinetics and HAMA formation were assessed via standard ELISAs. All assessments were made at pre-determined timepoints using validated assays at a central laboratory. The target pharmacodynamic marker CD3 as well peripheral leukocyte subsets were tracked daily and at day 7 and 14. CD3 counts exhibited dose dependent reductions. Results: TOL101 downmodulated the CD3 receptor complex on ab-TCR+ T cells in a dose related fashion while gd-TCR+ T cells, B cells, NK cells, granulocytes, and monocytes in the peripheral blood remained at baseline levels or increased slightly in number. TOL101 appears to act by binding reversibly to the ab-TCR receptor, with the presence of CD2+ T cells supporting a downmodulation of the TCR as opposed to depletion of peripheral blood alpha beta T-lymphocytes. Furthermore, memory and naive T cell populations were equally susceptible to TOL101 modulation. The pharmacokinetic profile of TOL101 correlated with the kinetics of the CD3+ pharmacodynamic marker. The ratio of CD4 to CD8 T cells as well as Memory to Naïve T cells appeared to return to base line 14 days after treatment commencement. Inflammatory cytokine and nitric oxide production was minimal following TOL101 infusion at all of the dose levels tested and no HAMA was detected. Conclusions: TOL101 is capable of specifically modulating ab-TCR+ T cells, having little effect on other immune cell subsets and no clinically significant cytokine release or HAMA formation at the dose ranges tested." @default.
• W2316508538 created "2016-06-24" @default.
• W2316508538 creator A5001501870 @default.
• W2316508538 creator A5016839655 @default.
• W2316508538 creator A5029407326 @default.
• W2316508538 creator A5030212073 @default.
• W2316508538 creator A5046927362 @default.
• W2316508538 creator A5060905691 @default.
• W2316508538 creator A5063030673 @default.
• W2316508538 creator A5066036858 @default.
• W2316508538 creator A5077468407 @default.
• W2316508538 creator A5089226253 @default.
• W2316508538 date "2012-11-01" @default.
• W2316508538 modified "2023-10-05" @default.
• W2316508538 title "TOL101- Anti-αβTCR Monoclonal Antibody Immune Monitoring During Initial Phase 2 Renal Transplant Trials" @default.
• W2316508538 doi "https://doi.org/10.1097/00007890-201211271-02301" @default.
• W2316508538 hasPublicationYear "2012" @default.
• W2316508538 type Work @default.
• W2316508538 sameAs 2316508538 @default.
• W2316508538 citedByCount "0" @default.
• W2316508538 crossrefType "journal-article" @default.
• W2316508538 hasAuthorship W2316508538A5001501870 @default.
• W2316508538 hasAuthorship W2316508538A5016839655 @default.
• W2316508538 hasAuthorship W2316508538A5029407326 @default.
• W2316508538 hasAuthorship W2316508538A5030212073 @default.
• W2316508538 hasAuthorship W2316508538A5046927362 @default.
• W2316508538 hasAuthorship W2316508538A5060905691 @default.
• W2316508538 hasAuthorship W2316508538A5063030673 @default.
• W2316508538 hasAuthorship W2316508538A5066036858 @default.
• W2316508538 hasAuthorship W2316508538A5077468407 @default.
• W2316508538 hasAuthorship W2316508538A5089226253 @default.
• W2316508538 hasBestOaLocation W23165085381 @default.
• W2316508538 hasConcept C114684123 @default.
• W2316508538 hasConcept C126322002 @default.
• W2316508538 hasConcept C159654299 @default.
• W2316508538 hasConcept C167672396 @default.
• W2316508538 hasConcept C19317047 @default.
• W2316508538 hasConcept C203014093 @default.
• W2316508538 hasConcept C2776090121 @default.
• W2316508538 hasConcept C2909675724 @default.
• W2316508538 hasConcept C2911091166 @default.
• W2316508538 hasConcept C542903549 @default.
• W2316508538 hasConcept C71924100 @default.
• W2316508538 hasConcept C8891405 @default.
• W2316508538 hasConcept C98274493 @default.
• W2316508538 hasConceptScore W2316508538C114684123 @default.
• W2316508538 hasConceptScore W2316508538C126322002 @default.
• W2316508538 hasConceptScore W2316508538C159654299 @default.
• W2316508538 hasConceptScore W2316508538C167672396 @default.
• W2316508538 hasConceptScore W2316508538C19317047 @default.
• W2316508538 hasConceptScore W2316508538C203014093 @default.
• W2316508538 hasConceptScore W2316508538C2776090121 @default.
• W2316508538 hasConceptScore W2316508538C2909675724 @default.
• W2316508538 hasConceptScore W2316508538C2911091166 @default.
• W2316508538 hasConceptScore W2316508538C542903549 @default.
• W2316508538 hasConceptScore W2316508538C71924100 @default.
• W2316508538 hasConceptScore W2316508538C8891405 @default.
• W2316508538 hasConceptScore W2316508538C98274493 @default.
• W2316508538 hasIssue "10S" @default.
• W2316508538 hasLocation W23165085381 @default.
• W2316508538 hasLocation W23165085382 @default.
• W2316508538 hasOpenAccess W2316508538 @default.
• W2316508538 hasPrimaryLocation W23165085381 @default.
• W2316508538 hasRelatedWork W1604264985 @default.
• W2316508538 hasRelatedWork W2003301929 @default.
• W2316508538 hasRelatedWork W2006922152 @default.
• W2316508538 hasRelatedWork W2053350302 @default.
• W2316508538 hasRelatedWork W2059422010 @default.
• W2316508538 hasRelatedWork W2085476683 @default.
• W2316508538 hasRelatedWork W2093020311 @default.
• W2316508538 hasRelatedWork W2108007089 @default.
• W2316508538 hasRelatedWork W2110363972 @default.
• W2316508538 hasRelatedWork W72712021 @default.
• W2316508538 hasVolume "94" @default.
• W2316508538 isParatext "false" @default.
• W2316508538 isRetracted "false" @default.
• W2316508538 magId "2316508538" @default.
• W2316508538 workType "article" @default.