2022年5月3日 · Here, we describe the design and characterization of a conditionally activated IL-2 prodrug, WTX-124, that takes advantage of the dysregulated protease milieu of tumors. WTX-124 was engineered as a single molecule containing an inactivation domain and a half-life extension domain that are tethered to a fully active IL-2 by protease-cleavable ...

Here, we describe the design and characterization of a conditionally activated IL-2 prodrug, WTX-124, that takes advantage of the dysregulated protease milieu of tumors.

2024年5月29日 · WTX-124 is a half-life extended, masked cytokine (INDUKINE molecule) rationally engineered to release wild type IL-2 in tumors. We previously reported that WTX-124 is clinically active as a monotherapy at doses safely administered in the outpatient setting.

• Our work shows that WTX-124, a pro-drug containing wild-type IL-2, is selectively processed and activated in tumors and is efficacious in murine models, even in the presence of regulatory T cells • WTX-124 activity is dependent on the processing of the pro-drug as a non-cleavable version of WTX-124 (WTX-124-NC) is not efficacious in our ...

2022年5月3日 · WTX-124, an IL-2 containing INDUKINE protein, was designed to enhance the clinical profile of rhIL-2 treatment by facilitating less frequent systemic delivery, increasing the tumor exposure of the molecule, and decreasing the toxicity associated with high-dose IL-2.

2023年11月3日 · Preliminary data on WTX-124 provide compelling early evidence of dose-dependent biomarker and antitumor activity in patients with advanced or metastatic solid tumors relapsed or refractory to standard of care therapy, including two patients with ongoing unconfirmed partial responses (uPR) in the highest dose tested to date, cohort 4 (12 mg) -

2022年6月15日 · To address these limitations, we designed WTX-124, an IL-2 pro-drug (IL-2 INDUKINE™ protein) that takes advantage of dysregulated protease activity in the tumor microenvironment (TME) to selectively release active IL-2 in …

To address this challenge, we engineered an IL-2 INDUKINETM molecule (WTX-124) to be administered systemically but selectively activated in the tumor microenvironment (TME) by dysregulated proteases. Distinct from other next-generation IL-2 molecules, WTX-124 is designed to release a fully potent, wild-type cytokine in tumors.

方法为了解决这些限制，我们设计了 WTX-124，一种 IL-2 前药（IL-2 INDUKINE™ 蛋白），它利用肿瘤微环境 (TME) 中失调的蛋白酶活性，在全身给药后选择性地将活性 IL-2 递送至肿瘤。 通过使用肿瘤蛋白酶敏感接头将细胞因子连接到失活结构域来实现外周失活。 INDUKINE™ 分子还设计有半衰期延长元件，以改善药代动力学特征并在肿瘤中保持更长的暴露时间。 一旦 IL-2 INDUKINE™ 蛋白到达肿瘤，肿瘤相关蛋白酶就会切割接头并释放完全活跃的细胞因子。 结果 …

2023年11月3日 · Preliminary data on WTX-124 provide compelling early evidence of dose-dependent biomarker and antitumor activity in patients with advanced or metastatic solid tumors relapsed or refractory to standard of care therapy, including two patients with ongoing unconfirmed partial responses (uPR) in the highest dose tested to date, cohort 4 (12 mg ...