Off-target refers to adverse effects as a result of modulation of other targets; these may be related biologically or totally unrelated to the target of interest. Both the risk assessment and development strategies used for xenobiotics are influenced by the understanding of the mechanism of toxicity...
但是它可以与肿瘤抗原与结合以外，还可以与正常组织上的某种抗原结合。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。
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...
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 ...
TCEs demonstrate impressive clinical activity in hematologic cancers and ‘cold’ solid tumors unresponsive to other immune therapies1,5,6. The clinical utility of current bispecific TCEs for the treatment of solid tumors is hampered by on-target, off-tumor toxicity, which limits the achievement ...
Although cancer vaccines have had acceptable tolerability so far, in many cases the vaccine was not efficacious and thus may have lacked potency. However, on-target off-tumor toxicity has been observed in clinical studies testing other therapies targeting TAAs. For instance, a chimeric antigen ...
One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity ...
Thus, the effects of pharmacological blockers used at high concentrations on cancer cells should be a mixture of on-target and off-target actions. Here, we compared the effects reported for TTCC blockers with the expected effects of Ca2+ channel block and preclusion of Ca2+ entry. Their ...
Traditionally drugs have been designed with the aim of targeting a single biological entity, usually a protein (the so-called “on-target”), with high selectivity to avoid any unwanted effects arising from mis-targeting other biological targets (“off-targets”). On this basis, the concept of...
A major challenge in the application of the CRISPR-Cas13d system is to accurately predict its guide-dependent on-target and off-target effect. Here, we perform CRISPR-Cas13d proliferation screens and design a deep learning model, named DeepCas13, to pred