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T cell-redirecting bispecific antibodies in cancer immunotherapy: recent advances

  • Lin Yu
  • Jianhua WangEmail author
Review – Clinical Oncology

Abstract

Purpose

Globally, cancer is a critical illness which seriously threatens human health. T-cell-based cancer immunotherapy for some patients has demonstrated impressive achievements including chimeric antigen receptor T cells, immune checkpoint inhibitors and T cell-redirecting bispecific antibodies (TRBAs). TRBAs recruit T cells to lyse cancer cells bypassing the antigen presentation through the major histocompatibility complex pathways. In this review we summarized the TRBAs formats, biophysical characteristics, the preclinical and clinical trial results, as well as the challenges faced by TRBAs in tumour therapy.

Methods

Herein the relevant literature and clinical trials from the PubMed and ClinicalTrials.gov database.

Results

The advances in protein engineering technology have generated diverse TRBAs format which can be classified into two categories: IgG-like TRBAs and non-IgG-like TRBAs. Multiple applications of TRBAs showed encouraging curative effect and entered clinical trials for lymphoid malignancy and solid tumour.

Conclusions

TRBA is a powerful tool for the cancer treatment and the clinical studies showed potent anti-tumour efficacy in hematologic malignancies. Although the clinical outcomes of TRBAs in solid tumours are less satisfied than hematologic malignancies, many preclinical antibodies and combination therapies are being evaluated

Keywords

Cancer immunotherapy Bispecific antibodies Redirected T cell Lymphoid malignancy Solid tumour 

Abbreviations

ADCC

Antibody-dependent cell-mediated cytotoxicity

ALL

Acute lymphoblastic leukemia

AML

Acute myelocytic leukemia

APCs

Antigen-presenting cells

ATC

Activated T cells

BiTE

Bispecific T-cell engagers

BsAb

Bispecific antibody

CAR-T

Chimeric antigen receptor T cells

CDC

Complement-dependent cytotoxicity

CEA

Carcinoembryonic antigen

CLL

Chronic lymphocytic leukemia

CR

Complete response

CRh

Complete response with partial hematopoietic recovery

DART

Dual-affinity re-targeting

DLBCL

Diffuse large B-cell lymphoma

EpCAM

Epithelial cell adhesion molecule

FAE

Fab-arm exchange

Fab

Fragment of antigen binding

FcγR

Fc-gamma receptors

Fv

Variable fragments

HER

Human epidermal growth factor receptor

ImmTAC

Immune-mobilising monoclonal T cell receptors against cancer

KiH

Knobs-into-holes

mCR

Macroscopic complete remission

MDS

Myelodysplastic syndrome

MHC

Major histocompatibility complex

MM

Multiple myeloma

MRD

Minimal residual disease

MTD

Maximum tolerated dose

NETs

Neuroendocrine tumours

NHL

Non-Hodgkin lymphoma

ORR

Overall response rate

OS

Overall survival

Ph−

Philadelphia chromosome negative

Ph+

Philadelphia chromosome positive

PSMA

Prostate-specific membrane antigen

ScFv

Single chain antibody variable fragments

SSTR2

Somatostatin receptor 2

SOC

Standard of care chemotherapy

TCR

T cell receptor

TRBAs

T cell-redirecting bispecific antibodies

Notes

Acknowledgements

This work was supported by the National Key Scientific Instrument and Equipment Development Project (No. 21827812) and the Foundation and Advanced Research Project of CQ CSTC (cstc2018jscx-mszd0280, cstc2017shms-xdny0033, cstc2013jjB0011).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no competing interests associated with the manuscript.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Biorheological Science and Technology (Ministry of Education), College of BioengineeringChongqing UniversityChongqingChina

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