denileukin diftitox

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Ligands
denileukin diftitox

GtoPdb Ligand ID: 7044

Synonyms: DAB389 IL2 | denileukin diftitox-cxdl | LY 335348 | Lymphir® | Ontak®

denileukin diftitox is an approved drug (FDA (1999))

Comment: Denileukin diftitox is an anti-cancer immunotherapy drug that was designed to target and eradicate malignant (IL-2 receptor-expressing) T cells. It is a recombinant protein containing peptide sequences of both interleukin-2 and diphtheria toxin [1,5]. It simultaneously directly kills IL-2R expressing tumour cells and promotes depletion of host Treg cells which enhances the immune response

References
1. Bacha P, Williams DP, Waters C, Williams JM, Murphy JR, Strom TB. (1988) Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein. J Exp Med, 167 (2): 612-22. [PMID:3126255]
2. Foley BT, Moehring JM, Moehring TJ. (1995) Mutations in the elongation factor 2 gene which confer resistance to diphtheria toxin and Pseudomonas exotoxin A. Genetic and biochemical analyses. J Biol Chem, 270 (39): 23218-25. [PMID:7559470]
3. Foss FM, Kim YH, Prince MM, Kuzel TM, Yannalou CK, Ooi CE, Xing D, Sauter N, Singh P, Czuczman M et al.. (2022) Efficacy and Safety of E7777 (improved purity Denileukin diftitox [ONTAK]) in Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma: Results from Pivotal Study 302. Blood, 140 (Supplement 1): 1491–1492. DOI: 10.1182/blood-2022-166916
4. Kawai H, Ando K, Maruyama D, Yamamoto K, Kiyohara E, Terui Y, Fukuhara N, Miyagaki T, Tokura Y, Sakata-Yanagimoto M et al.. (2021) Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma. Cancer Sci, 112 (6): 2426-2435. [PMID:33792128]
5. vanderSpek JC, Mindell JA, Finkelstein A, Murphy JR. (1993) Structure/function analysis of the transmembrane domain of DAB389-interleukin-2, an interleukin-2 receptor-targeted fusion toxin. The amphipathic helical region of the transmembrane domain is essential for the efficient delivery of the catalytic domain to the cytosol of target cells. J Biol Chem, 268 (16): 12077-82. [PMID:8505330]

References

1. Bacha P, Williams DP, Waters C, Williams JM, Murphy JR, Strom TB. (1988)
Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein.
J Exp Med, 167 (2): 612-22. [PMID:3126255]

2. Foley BT, Moehring JM, Moehring TJ. (1995)
Mutations in the elongation factor 2 gene which confer resistance to diphtheria toxin and Pseudomonas exotoxin A. Genetic and biochemical analyses.
J Biol Chem, 270 (39): 23218-25. [PMID:7559470]

3. Foss FM, Kim YH, Prince MM, Kuzel TM, Yannalou CK, Ooi CE, Xing D, Sauter N, Singh P, Czuczman M et al.. (2022)
Efficacy and Safety of E7777 (improved purity Denileukin diftitox [ONTAK]) in Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma: Results from Pivotal Study 302.
Blood, 140 (Supplement 1): 1491–1492. DOI: 10.1182/blood-2022-166916

4. Kawai H, Ando K, Maruyama D, Yamamoto K, Kiyohara E, Terui Y, Fukuhara N, Miyagaki T, Tokura Y, Sakata-Yanagimoto M et al.. (2021)
Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma.
Cancer Sci, 112 (6): 2426-2435. [PMID:33792128]

5. vanderSpek JC, Mindell JA, Finkelstein A, Murphy JR. (1993)
Structure/function analysis of the transmembrane domain of DAB389-interleukin-2, an interleukin-2 receptor-targeted fusion toxin. The amphipathic helical region of the transmembrane domain is essential for the efficient delivery of the catalytic domain to the cytosol of target cells.
J Biol Chem, 268 (16): 12077-82. [PMID:8505330]