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Review
. 2021 May 3;14(1):75.
doi: 10.1186/s13045-021-01084-4.

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

Zheng Tian #  1 , Ming Liu #  2   3   4 , Ya Zhang  5   6   7   8   9   10 , Xin Wang  11   12   13   14   15   16
Affiliations
Review

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

Zheng Tian et al. J Hematol Oncol. .

Abstract

Harnessing the power of immune cells, especially T cells, to enhance anti-tumor activities has become a promising strategy in clinical management of hematologic malignancies. The emerging bispecific antibodies (BsAbs), which recruit T cells to tumor cells, exemplified by bispecific T cell engagers (BiTEs), have facilitated the development of tumor immunotherapy. Here we discussed the advances and challenges in BiTE therapy developed for the treatment of hematologic malignancies. Blinatumomab, the first BiTE approved for the treatment of acute lymphocytic leukemia (ALL), is appreciated for its high efficacy and safety. Recent studies have focused on improving the efficacy of BiTEs by optimizing treatment regimens and refining the molecular structures of BiTEs. A considerable number of bispecific T cell-recruiting antibodies which are potentially effective in hematologic malignancies have been derived from BiTEs. The elucidation of mechanisms of BiTE action and neonatal techniques used for the construction of BsAbs can improve the treatment of hematological malignancies. This review summarized the features of bispecific T cell-recruiting antibodies for the treatment of hematologic malignancies with special focus on preclinical experiments and clinical studies.

Keywords: Bispecific T cell engager; Bispecific antibody; Cancer immunotherapy; Hematologic malignancy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Structures of bispecific T cell-recruiting antibodies. A bispecific T cell engager (BiTE) consists of two single-chain variable fragments (scFvs); a dual-affinity retargeting antibody (DART) consists of two engineered scFvs whose VH exchanged with the other one; a TandAb consists of two single-chain diabodies with four variable domains; a XmAb consists of one scFv, one Fab fragment and one hetero-Fc domain; a 2:1 Crossmab contains two tumor antigen binders and one CD3 binder; “knob in hole” technique and duobody technique enable production of bispecific antibodies with similar structures to natural IgG
Fig. 2
Fig. 2
Mechanisms of tumor cell lysis mediated by the BiTEs. BiTEs can redirect T cells to tumor cells and active T cells. Activated T cells release perforin and other granzymes through immunological synapses. These cytolytic proteins can form endosomes in tumor cells and lyse tumor cells ultimately
Fig. 3
Fig. 3
Targets of bispecific B cell-recruiting antibodies. CD19 and CD20 are targets for treatment of NHL; CD19 is the target for treatment of acute lymphocytic leukemia; CD123, CD33, CLEC12A, WT1, and FLT3 are targets for treatment of acute myeloid leukemia; BCMA, CD38, and GPRC5D are targets for treatment of multiple myeloma
See this image and copyright information in PMC

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