Explore T-Cell Bispecific Antibodies

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Overview

T-cell bispecifics are an innovative method of harnessing the immune system to fight cancer

Tumours may employ various mechanisms that result in an insufficient number of activated and/or antigen-specific T cells within the tumour microenvironment.1 One approach to redirect and expand populations of T cells is the development of T-cell bispecific antibodies, which can engage any type of T cell, independent of their antigen specificity to cancer cells.2-4

T-cell bispecific antibodies use recombinant antibody–based technology to simultaneously bind to CD3ε, a component of the T-cell receptor (TCR) complex, and to a tumour antigen (TA). Simultaneous binding of a T-cell bispecific antibody to a T cell and a tumour cell results in crosslinking of the TCR, subsequent downstream signalling, and formation of an immunological synapse that results in tumour killing through4

  • T-cell activation and secretion of cytotoxic granules
  • T-cell activation and secretion of cytokines/chemokines that generate a pro-inflammatory tumour microenvironment and recruit additional T cells from the circulation
  • T-cell proliferation and expansion at the tumour site

T-cell bispecific bond

T-cell bispecific antibody–mediated tumour-cell killing does not require antigen presentation and is independent of T-cell specificity, activation, and differentiation status.4,5 Therefore, T-cell bispecific antibodies may be used to promote antitumour immune activity while bypassing steps in the cancer immunity cycle.4,6,7

 
Platforms

Roche is exploring the potential of 2 innovative T-cell bispecific antibody platforms in reinitiating antitumour immune responses across various tumour types

 

  • 2:1 TCB TECHNOLOGY
  • 1:1 TDB TECHNOLOGY
2:1 TCB TECHNOLOGY

The 2:1 T-Cell Bispecific (TCB) platform represents a novel approach to reviving T-cell–mediated immune responses in a variety of tumours


Roche’s 2:1 TCB technology facilitates bivalent binding to a tumour antigen (TA) and monovalent binding to the CD3ε subunit of the T-cell receptor (TCR) complex.4 The 2:1 TCB antibody is equipped with structural features that promote tumour targeting and retention, resulting in a robust, antitumour effect.7

T-cell bispecific

1:1 TDB TECHNOLOGY

The 1:1 T-cell Dependent Bispecific (TDB) platform utilises native antibody architecture to revive T-cell–mediated immune responses in a variety of tumours


Roche’s 1:1 TDB technology facilitates simultaneous binding to a tumour antigen (TA) and to CD3ɛ on T cells. The 1:1 TDB antibody is equipped with structural features that promote T-cell recruitment and retention, resulting in a robust, antitumour effect.8,9

T-cell Dependent Bispecific

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References 
  1. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321-330. PMID: 28102259
  2. Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20:838-847. PMID: 25728220
  3. Frankel SR, Baeuerle PA. Targeting T cells to tumour cells using bispecific antibodies. Curr Opin Chem Biol. 2013;17:385-392. PMID: 23623807
  4. Bacac M, Klein C, Umana P. CEA TCB: a novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumours. Oncoimmunology. 2016;5:e1203498. PMID: 27622073
  5. Davis MM. A new trigger for T cells. Cell. 2002;110:285-287. PMID: 12176315
  6. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1-10. PMID: 23890059
  7. Bacac M, Fauti T, Sam J, et al. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumours. Clin Cancer Res. 2016;22:3286-3297. PMID: 26861458
  8. Sun LL, Ellerman D, Mathieu M, et al.  Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015;7:1-10. PMID: 25972002
  9. Sun LL, Wang P, Clark R, et al. Preclinical characterization of combinability and potential synergy of anti-CD20/CD3 T-cell dependent bispecific antibody with chemotherapy and PD-1/PD-L1 blockade. Blood. 2016;128:4168.

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