可切割的linker的蛋白酶 在健康组织中,Probody抗体基本上保持完整,Masking peptide阻止了抗体和靶点结合,避免了off-tumor的副作用。当Probody到达肿瘤微环境,肿瘤相关蛋白酶切割底物linker,去除掩蔽肽,抗体结合靶抗原。 基于Probody技术抗体药物开发 C...
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。
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. ...
1. 公司研发的经CAB(Conditionally Active Biologics)技术改造的抗体接触到酸性条件下靶点(肿瘤微环境为酸性环境),才会被激活,且激活是可逆的,能解决抗体类药物的on-target正常组织毒性问题(on-target, off-tumor toxicity),这一技术能应用于抗体药、ADC、CART、蛋白等不同生物类药物的研发,也能用于炎症,自身免疫疾病...
This technology opens another avenue to safely target a variety of other TAA by CAR-T even when there is the potential of on-target off-tumor toxicity in normal tissues for those antigens.shuangshuang zhangSuzhou Immunofoco Biotechnology Co., Ltd, Shanghai, shanghai, ChinaRuidong Hao...
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 ...
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 ...
The proteolytically activated, unmasked HER2-TCE demonstrated highly potent cytotoxicity against high HER2-expressing tumor cells, SKOV3 (∼650,000 HER2 receptors per cell; Fig. 2b) and BT-474 (∼975,000 HER2 receptors per cell; Fig. 2c), showing nearly complete target cell killing with ...
However, on-target off-tumor toxicity has been observed in clinical studies testing other therapies targeting TAAs. For instance, a chimeric antigen receptor-engineered T cell therapy (CAR-T) targeting the colorectal carcinoembryonic antigen (CEA) caused severe colitis in a high percentage of ...
Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a ...