denileukin diftitox

Denileukin diftitox (DAB 389IL-2) is a diphtheria toxin (DT)-related interleukin 2 (IL-2) fusion protein toxin that depletes cells expressing the high-affinity form of the IL-2 receptor (IL-2R), CD25. Denileukin diftitox binds to cells expressing IL-2R and inhibits protein synthesis through internalization of the diphtheria toxin fragment[1][2][3].

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> Interleukin Related

IL-2 receptor (IL-2R), CD25[1]

Denileukin diftitox (DAB 389IL-2) 是一种 3 结构域融合蛋白毒素，由白喉毒素 (DT) 催化结构域、白喉毒素 (DT) 膜易位结构域和取代天然白喉毒素 (DT) 受体结合结构域的人 IL-2 组成[1]。 Denileukin diftitox (1-1000 pM; HUT 102/6TG 细胞) 对于体外携带高亲和力 IL-2 受体的细胞系细胞毒效力增加了大约 17 倍[3]。

Denileukin diftitox (DAB 389IL-2; 35 μg/kg; i.p.; 感染 H37Rv 的 C57BL/6 小鼠) 在小鼠模型中抑制分枝杆菌复制并降低 Treg 和髓源性抑制细胞 (MDSC) 的频率[1]。 Denileukin diftitox (2.5 或 3 μg/头; i.v.) 在小鼠模型中具有抗肿瘤活性并抑制肿瘤生长[2]。 Animal Model: C57BL/6 mice with infected H37Rv[1] Dosage: 35 μg/kg Administration: Intraperitoneal injection; twice a week, for 2 weeks Result: Reduced the colony-forming unit (CFU) numbers in lungs and spleens. Reduces Treg and MDSC frequencies in lungs and spleens. Animal Model: Female BALB/c mice with tumor models[2] Dosage: 2.5 or 3 μg/head Administration: Intravenous injection; weekly, for 2 or 3 weeks Result: Inhibited the growth of tumors.

[1]. Gupta S, et, al. Suppressor Cell-Depleting Immunotherapy With Denileukin Diftitox is an Effective Host-Directed Therapy for Tuberculosis. J Infect Dis. 2017 Jun 15;215(12):1883-1887.  

[2]. Albu DI, et, al. Preclinical immune antitumor activity of myeloid-targeting E7046 and Treg depleting E7777. Cancer Immunol Res (2016) 4 (1_Supplement): B034.

[3]. Kiyokawa T, et, al. Protein engineering of diphtheria-toxin-related interleukin-2 fusion toxins to increase cytotoxic potency for high-affinity IL-2-receptor-bearing target cells. Protein Eng. 1991 Apr;4(4):463-8.