The BiTE® molecule recruits a T cell to a cancer cell, leading to the formation of a cytolytic synapse4,10
The T cell becomes activated, releasing perforin and granzymes; fusion of perforin with the cancer cell membrane allows granzymes to enter the cancer cell to induce apoptosis9,10
Following cancer cell apoptosis, activated T cells release cytokines and produce additional perforin and granzymes that may allow T cells to target surrounding cancer cells; this potentially results in the serial lysis of multiple cancer cells by a single T cell4,10,11
Sustained activation of a single activated cytotoxic T cell theoretically results in local proliferation and expansion of polyclonal memory T cells4,10,12
Amgen is a pioneer in the development of immuno-oncology therapies. The BiTE® immuno-oncology platform continues to be investigated across multiple different hematologic malignancies and solid tumors.8,14
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.References ▼
1. Ok CY, Young KH. Checkpoint inhibitors in hematological malignancies. J Hematol Oncol. 2017;10(1):103. 2. Baudino TA. Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol. 2015;12(1):3-20. 3. Shekarian T, Valsesia-Wittmann S, Caux C, Marabelle A. Paradigm shift in oncology: targeting the immune system rather than cancer cells. Mutagenesis. 2015;30(2):205-211. 4. 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. 5. Ferrone S, Whiteside TL. Tumor microenvironment and immune escape. Surg Oncol Clin N Am. 2007;16:755-774. 6. Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol. 2007;25(4):267-296. 7. Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013;17(3):385-392. 8. 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. 9. Baeuerle PA, Reinhardt C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 2009;69(12):4941-4944. 10. Nagorsen D, Baeuerle PA. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res. 2011;317(9):1255-1260. 11. Ross SL, Sherman M, McElroy PL, et al. Bispecific T cell engager (BiTE®) antibody constructs can mediate bystander tumor cell killing. PLoS One. 2017;12(8):e0183390. 12. 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. 13. Q2 2019 pipeline, Amgen. https://www.amgenpipeline.com/~/media/amgen/full/www-amgenpipeline-com/charts/amgen-pipeline-chart.ashx. Accessed 8/1/2019. 14. FDA approves BLINCYTO® (blinatumomab) to treat minimal residual disease-positive B-cell precursor acute lymphoblastic leukemia in adults and children [press release]. Thousand Oaks, California. Press; August 1, 2019.