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

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.

The PD-1/PD-L1 Checkpoint in Normal Germinal Centers and Diffuse Large B-Cell Lymphomas

“…On the other hand, instead of unique targeting of immune cells, bispecific antibodies targeting two antigens simultaneously are innovative synthetic constructions rapidly developing for the management of hematologic malignancies [ 195 ]. Frequently, these bispecific antibodies target one tumour antigen (e.g., CD19 or CD20 in B-cell lymphomas) and one immune-related molecule (e.g., CD3), aiming at redirecting T cells against tumour cells and working as cytotoxic T-cell engagers [ 196 ].…”

Promoting the Effector Function of Natural Killer (NK) Cells with a Focus on Bispecific Redirecting Antibodies

“…Recently, T cell-redirecting bispecific antibodies (TR-BAs) have been of higher interest due to the promising preclinical and clinical outcomes (3,4). More specifically, a TRBA results from the fusion of two single-chain variable fragments (scFv) via a linker.…”

“…In the conventional TRBA, one of the scFvs is specific to a tumor marker of interest, and the other scFv recognizes and binds the CD3 receptor present on the T cells (3,4). As the other bispecific mAbs, TRBAs establish a bridge between the T cells and the malignant cells, against which one of their scFv is redirected.…”

“…This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. est (3,4). To date, several TRBAs developed against different target antigens involved in a series of oncological indications have been under preclinical and clinical investigation.…”

“…In addition to the aforementioned TRBAs, some other candidate therapeutics have also been developed using this platform to target different antigens, indicating different malignancies. For example, TRBAs against CD66e, EphA2, HER2, EGFR, CSPG4, and CD33 have been developed or are currently under development, highlighting the potential of this approach to developing potential therapeutics (3,4). Moreover, the other target antigens could also be considered to develop TRBAs against a wide range of solid and hematologic malignancies (all of which have been comprehensively discussed elsewhere) (6,7).…”