naptumomab estafenatox   Click here for help

GtoPdb Ligand ID: 9948

Synonyms: ABR-217620 | ABR217620 | Anyara (proposed trade name) | TTS CD3 | TTS-CD3
Immunopharmacology Ligand
Compound class: Antibody
Comment: Naptumomab estafenatox (ABR-217620) is an immuno-oncology clinical candidate biologic drug that is being developed by Active Biotech and NeoTX Therapeutics. It is a fusion protein containing a 5T4 (tumor-associated oncofetal trophoblast glycoprotein antigen) Fab moiety fused via the C terminus of the heavy chain to an engineered hybrid of Staphylococcus entertoxins A and E (SEA/E-120) superantigens [1]. Staphylococcal superantigens are secreted by the pathogen and stimulate a massive MHC class II-T cell receptor-mediated polyclonal T cell activation, which results in the release of large amounts of cytotoxic and proinflammatory cytokines and potent T-cell-mediated killing of tumour cells. Naptumomab estafenatox targets the destructive power of SEA/E-120 to 5T4-expressing tumour cells. The SEA/E-120 moiety is engineered to reduce MHC class II binding affinity so as to reduce killing of bystander MHC class II positive cells.
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References
1. Eisen T, Hedlund G, Forsberg G, Hawkins R. (2014)
Naptumomab estafenatox: targeted immunotherapy with a novel immunotoxin.
Curr Oncol Rep, 16 (2): 370. [PMID:24445502]
2. Elkord E, Burt DJ, Sundstedt A, Nordle Ö, Hedlund G, Hawkins RE. (2015)
Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α.
Oncotarget, 6 (6): 4428-39. [PMID:25669986]
3. Forsberg G, Skartved NJ, Wallén-Ohman M, Nyhlén HC, Behm K, Hedlund G, Nederman T. (2010)
Naptumomab estafenatox, an engineered antibody-superantigen fusion protein with low toxicity and reduced antigenicity.
J Immunother, 33 (5): 492-9. [PMID:20463598]
4. Hawkins RE, Gore M, Shparyk Y, Bondar V, Gladkov O, Ganev T, Harza M, Polenkov S, Bondarenko I, Karlov P et al.. (2016)
A Randomized Phase II/III Study of Naptumomab Estafenatox + IFNα versus IFNα in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis.
Clin Cancer Res, 22 (13): 3172-81. [PMID:26851187]