Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer

Figures & data

Figure 1. BiTE antibody constructs are generated by genetically linking minimal binding domains of mAbs for CD3 on T-cells and for surface antigens on target cancer cells onto a single polypeptide chain [8].

Figure 2. Engagement by BiTE antibody constructs leads to activation and polyclonal expansion of T-cells. The activation of T-cells requires the presence of target cells. Upon binding of the BiTE antibody construct to both CD3 on T-cells and the tumor-associated antigen on target cells, the formation of an immunological synapse is forced, thereby bypassing MHC/antigen-dependent activation of T-cells. Activation is achieved independently of TCR specificity, costimulation, or peptide antigen presentation. Subsequent to formation of the immunological synapse, apoptosis of the target cell is induced [8,9,27,28].

Table 1. Disease settings investigated with blinatumomab, a CD19-specific BiTE antibody construct.

Patient population	ClinicalTrials.gov identifier study code/acronym	Phase/study type	Study status*	N	Ref.
B-precursor ALL
Adult R/R B-precursor ALL	NCT01209286 MT103-206	2, Open label	Ongoing	36	[16]
Adult Philadelphia chromosome-negative R/R B-precursor ALL	NCT01466179 MT103-211	2, Open label, pivotal	Ongoing	189	[17]
Adult patients with R/R B-precursor ALL	NCT02013167 20120311/TOWER	3, Randomized, open label	Recruiting	n.a.	n.a.
Adult R/R Philadelphia chromosome-positive B-precursor ALL	NCT02000427 20120216/Alcantara	2, Open label	Recruiting	n.a.	n.a.
Pediatric and adolescent R/R B-precursor ALL	NCT01471782 MT103-205	1/2, Open label	Ongoing	93	[18]
Younger (1-30 years) patients with relapsed B-cell ALL	NCT02101853 COGAALL1331	3, Risk stratified, randomized,	Recruiting	n.a.	n.a.
Newly diagnosed BCR-ABL-negative B lineage ALL	NCT02003222 EGOG1910	3, Randomized, open label	Recruiting	n.a.	n.a.
Elderly newly diagnosed ALL	NCT02143414 SWOG S1318	2, Open label	Not yet recruiting	n.a.	n.a.
Adult MRD of B-precursor ALL	NCT00560794 MT103-202	2, Open label	Completed	21	[13,14]
Adult MRD of B-precursor ALL	NCT01207388 MT103-203/BLAST	2, Open label, EU pivotal	Ongoing	116	[15]
NHL
Patients with relapsed NHL	NCT00274742 MT103-104	1, Cohort	Completed	76	[11]
Patients with R/R DLBCL	NCT01741792 MT103-208	2, Open label	Ongoing	25	[19]

*According to clinicaltrials.gov.

Adapted with permissions from Zimmerman et al. [12].

ALL: Acute lymphoblastic leukemia; BiTE: Bispecific T-cell engager; DLBCL: Diffuse Large B-Cell Lymphoma; MRD: Minimal residual disease; NHL: Non-Hodgkin’s lymphoma R/R: Relapsed/refractory.

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