BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

De­spite rapid ad­vances in the field of im­muno-on­col­o­gy that have trans­formed the can­cer treat­ment land­scape, many can­cer pa­tients are still left be­hind.1,2 Not every per­son has ac­cess to in­no­v­a­tive ther­a­pies de­signed specif­i­cal­ly to treat his or her dis­ease. Many cur­rent­ly avail­able im­muno-on­col­o­gy-based ap­proach­es and chemother­a­pies have brought long-term ben­e­fits to some pa­tients — but many pa­tients still need oth­er ther­a­peu­tic op­tions.3

The phar­ma in­dus­try strives to im­prove clin­i­cal ben­e­fit, en­hance tol­er­a­bil­i­ty and max­i­mize ac­cess in tu­mors where ad­vances have demon­strat­ed ac­tiv­i­ty.1,2 Am­gen On­col­o­gy, one of the lead­ing de­vel­op­ers of in­no­v­a­tive ther­a­pies for nov­el tar­gets in dif­fi­cult-to-treat can­cers, is work­ing to bring new hope for trans­form­ing clin­i­cal out­comes for pa­tients with very few op­tions. One tech­nol­o­gy with the po­ten­tial to ad­vance im­muno-on­col­o­gy is Am­gen’s Bis­pe­cif­ic T Cell En­gager or BiTE®— plat­form. At Am­gen we are ex­plor­ing this tech­nol­o­gy across both sol­id tu­mor and hema­to­log­i­cal ma­lig­nan­cies.

Al­though T cells seek out ma­lig­nant cells, can­cer cells have de­vel­oped so­phis­ti­cat­ed mech­a­nisms to evade de­tec­tion and es­cape T cells.4,5 More­over, the ma­jor­i­ty of T cells are not di­rect­ed against ma­lig­nant cells and thus nat­u­ral­ly not ca­pa­ble of fight­ing can­cer. BiTE® is a tar­get­ed im­muno-on­col­o­gy plat­form en­gi­neered to en­gage against can­cer not on­ly the mi­nor­i­ty of T cells nat­u­ral­ly di­rect­ed against ma­lig­nant cells but al­so the ma­jor­i­ty of a pa­tient’s T cells nat­u­ral­ly not ca­pa­ble of fight­ing can­cer.6 The rea­son the mol­e­cule is called “bis­pe­cif­ic” is that it’s en­gi­neered from not one but two an­ti­bod­ies: One is de­signed to en­gage with CD3, which is found on T cells. The oth­er is de­signed to en­gage with a se­lect­ed tu­mor an­ti-gen, such as BC­MA, CD19, CD33, DLL3, MUC17, FLT3, CLDN18.2 or PS­MA. T cells on­ly be­come ac­ti­vat­ed and pro­lif­er­ate with the re­lease of cy­tokines, with the goal of on­ly stay­ing ac­ti­vat­ed if they en­counter can­cer cells in the pres­ence of BiTE®.

BiTE® tech­nol­o­gy has been stud­ied in thou­sands of pa­tients, in­clud­ing in­di­vid­u­als who have been fol­lowed for as long as five years.8,9

Clear­ly, the un­met need to en­hance pa­tient out­comes re­mains sig­nif­i­cant. Am­gen is com­mit­ted to de­liv­er­ing new ther­a­pies for pa­tients with com­plex can­cers. One po­ten­tial of the BiTE® im­muno-on­col­o­gy plat­form is that pa­tients may be able to ini­ti­ate treat­ment prompt­ly, be­cause BiTE® does not de­pend on the ex vi­vo ma­nip­u­la­tion of a pa­tient’s T cells.7 This ver­sa­tile tech­nol­o­gy is de­signed to treat tu­mors through many tu­mor as­so­ci­at­ed anti­gens, so Am­gen is in­ves­ti­gat­ing dozens of BiTE® mol­e­cules across both sol­id and hema­to­log­i­cal ma­lig­nan­cies — in­clud­ing a DLL3-tar­get­ed BiTE® mol­e­cule in small-cell lung can­cer, a BC­MA-tar­get­ed BiTE® mol­e­cule in mul­ti­ple myelo­ma, a PS­MA tar­get­ed BiTE® mol­e­cule in prostate can­cer, and CD33 and FLT3-tar­get­ed BiTE® mol­e­cules in acute myeloid leukemia.10 Re­searchers are in­ves­ti­gat­ing these mol­e­cules in pa­tients with high and low tu­mor bur­den across dif­fer­ent age groups, in those with rapid­ly pro­gress­ing dis­ease and across dif­fer­ent treat­ment lines.6 They hope these mol­e­cules can be used with the po­ten­tial to en­hance ac­tiv­i­ty in com­bi­na­tion with oth­er treat­ments.11

Cur­rent im­muno-on­col­o­gy ther­a­pies still aren’t ef­fec­tive in all pa­tients and tu­mor types, and many peo­ple with hema­to­log­ic ma­lig­nan­cies and sol­id tu­mors need dif­fer­ent and tar­get­ed treat­ment op­tions.1 Am­gen is work­ing to meet that need. The ther­a­peu­tic po­ten­tial that im­muno-on­col­o­gy hopes to de­liv­er is al­ways grow­ing, fu­eled by the vi­sion that dri­ves am­bi­tious re­search. Know­ing that con­nec­tion, and the stakes for pa­tients and their fam­i­lies, keeps Am­gen fo­cused on the next fron­tier.

Vis­it AmgenOn­col­o­ to learn more about the BiTE® plat­form and Am­gen’s pur­suit of in­no­v­a­tive tar­gets in dif­fi­cult-to-treat tu­mor types.


1. Ven­to­la CL. P T. 2017; 42:514-521.
2. Gomes-Sil­va D., et al. Biotech­nol J. 2018;13:1700097. doi:10.1002/biot.201700097.
3. Baudi­no TA. Curr Drug Dis­cov Tech­nol. 2015;12:3-20.
4. Fer­rone S, White­side TL. Surg On­col Clin N Am. 2007; 16:755-774.
5. Ra­bi­novich GA, Gabrilovich D, So­tomay­or EM. An­nu Rev Im­munol. 2007;25(4):267-296.
6. Yuraszeck T., et al. Clin Phar­ma­col Ther. 2017;101:634-645.
7. Ein­se­le, H., et al. Can­cer. 2020; 0 :1-10.
8. Da­ta on File, Am­gen; 2020.
9. Goek­buget N., et al. EHA. Ab­stract 1426.2020.
10. Q1 2020 pipeline, Am­gen.­gen­­dia/themes/am­gen/am­gen­pipeline-com/am­gen­pipeline-com/pdf/am­gen-pipeline-chart.pdf. Ac­cessed May 12, 2020.
11. Sedykh SE., et al. Drug Des De­v­el Ther. 2018;12:195-208.


Peter Kufer

Vice President & Innovator of BiTE® Technology, Amgen