HLE BiTE® technology: enhancing features of the BiTE® platform
Engineering BiTE® molecules to have a longer half-life
Bispecific T-cell Engager (BiTE®) technology is designed to overcome cancer cells’ evasion of the immune system by engaging patients’ own T cells to directly target cancer cells.1,2 BiTE® molecules are engineered to bind a selected tumor-associated antigen and CD3 found on T cells.3,4 Canonical BiTE® molecules are relatively small recombinant proteins that can be eliminated by the kidneys and have a typical serum half-life of a few hours.3,5
Currently, Amgen is designing half-life extended (HLE) BiTE® molecules containing a fragment crystallizable (Fc) domain.6 Adding an Fc domain to a BiTE® molecule is designed to increase the amount of time before it is eliminated from the body.7,8
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Extending the benefits of BiTE® technology
Canonical BiTE® molecules are relatively small recombinant proteins that can be eliminated by the kidneys and have a serum half-life of a few hours. Currently, the protein engineers at Amgen are designing BiTE® molecules with enhanced features, including a half-life extended (HLE) BiTE® molecule containing an Fc domain. Adding an Fc domain to the BiTE® molecule is designed to increase the amount of time before it is eliminated from the body.1-3,5-7
BiTE: Bispecific T-cell Engager; DLL3: delta-like protein 3; FLT3: FMS-like tyrosine kinase 3; GEJ: gastroesophageal junction; HLE: half-life extended; MUC17: mucin17; PSMA: prostate-specific membrane antigen.
1. Baeuerle PA, Kufer P, Bargou R. Curr Opin Mol Ther. 2009;11(1):22-30. 2. Frankel SR, Baeuerle PA. Curr Opin Chem Biol. 2013;17(3):385-392. 3. Yuraszeck T, Kasichayanula S, Benjamin JE. Clin Pharmacol Ther. 2017;101(5):634-645. 4. Nagorsen D, Baeuerle PA. Exp Cell Res. 2011;317(9):1255-1260. 5. Thakur A, Huang M, Lum LG. Blood Rev. 2018;32(4):339-347. 6. Raum T, Münz M, Brozy J, inventors. US Patent 2017/0218077A1. 8/3/2017. 7. Weidle UH, Tiefenthaler G, Weiss EH, et al. Cancer Genomics Proteomics. 2013;10(1):1-18. 8. Arvedson TL, Balazs M, Bogner P, et al. Cancer Res. 2017;77(suppl 13):Abstract 55.