HLE BiTE® technology: enhancing features of the BiTE® platform
Engaging the natural power of T cells with BiTE® Technology
BiTE® technology is designed to overcome cancer cells' evasion of the immune system by engaging patients own T cells to directly target cancer cells. BiTE® molecules are engineered to target a selected tumor antigen and CD3 found on T cells.1,3
BiTE® technology has been shown to activate the cytotoxic potential of T cells and lead to sustained T cell response and cancer cell apoptosis.1,4
Extending the benefits of BiTE® technology
Canonical BiTE® molecules are designed to be relatively small recombinant proteins that are cleared through the kidney, with 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 a fragment-crystallizable (Fc) domain. Adding an Fc portion to the BiTE® molecule is designed to extend the amount of time before it is eliminated from the body.1-3,5-7
It is anticipated that these HLE BiTE® molecules could potentially be infused less frequently.7,8
BCMA: B cell maturation antigen; BiTE: Bispecific T Cell Engager; CD: cluster of differentiation; DLL3: delta-like canonical Notch ligand 3; EGFR: epidermal growth factor receptor; FLT3: fms-like tyrosine kinase 3; HLE: half-life extended; PSMA: prostate-specific membrane antigen.
1. Baeuerle PA, Kufer P, Bargou R. BiTE: teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther. 2009;11(1):22-30. 2. Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013;17(3):385-392. 3. Yuraszeck T, Kasichayanula S, Benjamin JE. Translation and clinical development of bispecific T-cell engaging antibodies for cancer treatment. Clin Pharmacol Ther. 2017;101(5):634-645. 4. Nagorsen D, Baeuerle PA. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res. 2011;317(9):1255-1260. 5. Thakur A, Huang M, Lum LG. Bispecific antibody based therapeutics: strengths and challenges. Blood Rev. 2018;32(4):339-347. 6. Raum T, Münz M, Brozy J, inventors. BCMA and CD3 bispecific T cell engaging antibody constructs. US Patent 2017/0218077 A1. August 3, 2017. 7. Weidle UH, Tiefenthaler G, Weiss EH, Georges G, Brinkmann U. The intriguing options of multispecific antibody formats for treatment of cancer. Cancer Genomics Proteomics. 2013;10(1):1-18. 8. Arvedson TL, Balazs M, Bogner P, et al. Generation of half-life extended anti-CD33 BiTE® antibody constructs compatible with once-weekly dosing. Cancer Res. 2017;77(suppl 13):Abstract 55. 9. Ferrone S, Whiteside TL. Tumor microenvironment and immune escape. Surg Oncol Clin N Am. 2007;16:755-774. 10. Baeuerle PA, Reinhardt C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 2009;69(12):4941-4944. 11. Brischwein K, Schlereth B, Guller B, et al. MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. Mol Immunol. 2006;43(8):1129-1143. 12. Q2 2019 pipeline, Amgen. https://www.amgenpipeline.com/~/media/amgen/full/www-amgenpipeline-com/charts/amgen-pipeline-chart.ashx. Accessed 8/1/2019.