Investigative toxicology undertakes hypothesis-based research to understanda particular mode or mechanism of toxicity of concern and tp develop biomarkers that are relevant for clinical monitoring. These studies are often used to determine the species-specificity of an effect, to develop a counter-screen...
1.Karen A. Autio et al,Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology,Clin Cancer Res 2020;26:984–9 2.Polu KR, Lowman ...
这种正常组织上的抗原可以与这种药物靶向结合，即为on target，但是又不在肿瘤上，即off tumor。药物靶向识别正常组织上的抗原，会损伤机体正常组织，产生副作用，即on target-off tumor toxicity。
KingwellKatieNat Rev Drug DiscovNature Reviews Drug DiscoveryKingwell, K. Pioneering biased ligand offers efficacy with reduced on-target toxicity. Nat Rev Drug Discov 14, 809-810 (2015).K. Kingwell, Pioneering biased ligand offers efficacy with reduced on-target toxicity, Nat. Rev. Drug Discov....
1.Karen A. Autio et al,Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology,Clin Cancer Res 2020;26:984–9 2.Polu KR, Lowman HB. Probody therapeutics for targeting antibodies to diseased tissue....
Adverse toxicologic effects are categorized as chemical-based, on-target, or off-target effects. Chemical-based toxicity is defined as toxicity that is related to the physicochemical characteristics of a compound and its effects on cellular organelles, membranes, and/or metabolic pathways. On-target ...
This report shows that CAIX-targeting CAR T cells exerted antigen-specific effects in vivo and induced liver toxicity at the lowest dose of 0.2 × 109 T cells applied, illustrating the potency of receptor-modified T cells. We provide in-patient proof that the observed "on-target" toxicity ...
Ocular-toxicityThe heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of ~400 client proteins, many of which contribute to oncogenesis. As a result, Hsp90 pan-inhibitors, which inhibit all four Hsp90 isoforms, have been investigated in the clinic ...
And importantly, both therapies were well tolerated as there were no reports of cytokine syndrome release Grade 2 or higher, and no serious adverse events, dose-limiting toxicities nor on-target off-tumor toxicity, adds the analyst. Celyad target lowered to $48 on new launch timeline at H.C...
POSTER PRESENTATION Open AccessOn-target off-tumor toxicity; when enhancing anNKG2D-based CAR in vitro led to severe toxicitiesin vivoHeather VanSeggelen 1 , Joanne A Hammill 1* , Daniela GM Tantalo 1 , Carole Evelegh 1 , Galina F Denisova 1 ,Brian Rabinovich 2 , Jacek M Kwiecien 1 ...