On-target off-tumor toxicity

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August undefined, 2024

Web4 de abr. de 2024 · To address this issue, and to avoid on-target off-tumor toxicities, we developed a Trop2-targeting ProTriTAC™ (Protease-activated Tri-specific T cell Activating Construct), a T cell engager ... Web3 de mai. de 2024 · Abstract Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor …

On-target and Off-target-based Toxicologic Effects - SAGE Journals

Web18 de fev. de 2024 · For instance, toxicities such as cytokine release syndrome and immune escape mechanisms including loss of the antigen under CART-mediated … Webwww.ncbi.nlm.nih.gov philibert as d\u0027or

Masking bispecific T cell engagers until they reach the tumor …

WebNational Center for Biotechnology Information Webon-target, or off-target. The objective of this session at the 2012 Society of Toxicologic Pathologists Symposium in Boston, Massachusetts, was to discuss chemical-based, on … WebHowever, target antigens are often expressed on both tumor cells and healthy tissues, raising concerns regarding on-target, off-tumor toxicity. 41 The severity of toxic manifestations depends on how accessible, widespread, and vital the target tissue is. philibertblackbook

CAR-T cell therapy: current limitations and potential …

Time to evolve: predicting engineered T cell-associated toxicity …

WebA Novel Mouse Model Using Optical Imaging to Detect On-target, Off-tumor CAR-T Cell Toxicity Introduction Cancer remains the second leading cause of death globally, despite the recent explosion of cancer immunotherapeutics that have significantly improved patient outcome for certain tumor types. Web19 de abr. de 2024 · An elegant demonstration of “on-target, off-tumor” toxicity was the development of CAR-T cells targeting carboxy-anhydrase-IX (CA IX) [ 10 ]. CA IX is expressed by many renal cell carcinomas, but low expression can also be found in normal tissue, including bile duct. philibert autobusWebThe toxicity of TCR-Ts can come from three aspects: (1) the on-target/off tumor toxicity due to the low level expression of shared-tumor antigen in normal tissues ( 8, 9 ); (2) the off-target toxicity due to the TCR’s promiscuous recognition of unrelated epitopes derived from normal proteins ( 12, 13, 17 ); and (3) the alloreactivity of TCR-Ts … philibert bacot

"WebA major risk and the direct cause of adverse effects reported in clinical and preclinical trials is off-tumor, on-target toxicity due to expression of the target antigen on nontumor tissues. " - On-target off-tumor toxicity

On-target off-tumor toxicity

Toxicity and management in CAR T-cell therapy - PMC

Web2 de ago. de 2024 · A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization. Chimeric antigen receptors … Web1 de nov. de 2024 · Antitumor efficacy is often accompanied by hematopoietic toxicity due to shared antigen expression within the hematopoietic system ( 13–18 ), although many have reasoned that hematopoietic toxicity is acceptable if AML CAR T-cell therapy is administered in the context of myeloablation as a bridge to hematopoietic cell transplant …

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Web16 de jun. de 2024 · On-target, off-tumor toxicity can be reduced by using CAR targeting systems that can improve the recognition of tumor cells ( 5 ). One such strategy is to … Web25 de mai. de 2015 · 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。

Web25 de nov. de 2024 · Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma Antitumor activity without on … Web11 de abr. de 2024 · where ei and pi represent the i-th physico-chemical property of the amino acids from peptides e and p, and n is equal to the target peptide length. 5. mRNA …

Web11 de set. de 2013 · On-target side effects refer to the pharmacodynamic effect on normal tissues that occurs when the target that's being inhibited in the tumor is also being … Web10 de abr. de 2024 · Without tumor antigen specificity, the risk of significant on-target off-tumor toxicity increases substantially. 4 To overcome the immunosuppressant environment in malignant diseases,...

Web12 de abr. de 2024 · One strategy to mitigate on-target, off-tumor toxicity is to fine-tune the affinity of CARs, such that healthy non-malignant tissues with basal antigen expression are spared, whereas tumor...

Web19 de out. de 2012 · 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. philibert battletechWeb19 de out. de 2012 · Adverse toxicologic effects are categorized as chemical-based, on-target, or off-target effects. Chemical-based toxicity is defined as toxicity that is … philibert babouWebto predict on-target, off-tumor toxicity, highlighting the need for an animal model that expresses human targets in normal tissue.6 One method under investigation to improve … philibert bernard philibert boisWeb15 de fev. de 2024 · HER2-PAT (cleaved XPAT) demonstrated potent in vitro tumor-directed T-cell cytotoxicity (EC50 1-2pM) and target-dependent T-cell activation and production of cytokines by PBMCs. HER2-PAT also exhibited cytotoxicity in HR+, HER2 1+ MCF7s at higher doses (EC50 0.13nM). philibert bolt actionWeb21 de nov. de 2014 · “On-target off-tumor” toxicity may occur when TCRs fail to discriminate levels of TAAs presented on normal versus tumor cells. For example, toxicity occurs when the antigen is expressed equally, or when the TCR not only recognizes low levels of the targeted TAA epitope, but also a cross-reactive epitope expressed on … philibert bressonWeb30 de mar. de 2024 · In this issue of Nature Cancer, Cattaruzza et al. 5 address the on-target off-tumor toxicity and limited therapeutic indices of TCEs in solid tumors by … philibert boonlake