Delving into the Latest Updates on Anti-HER2/CD3/CD28 trispecific antibody(Sanofi) with Synapse

Overview

Basic Info

Drug Type

Trispecific T-cell engager (TriTE)

Synonyms-

Target

CD28 x CD3 x HER2

Action

agonists, stimulants, antagonists

Mechanism

CD28 agonists(T-cell-specific surface glycoprotein CD28 agonists), CD3 stimulants(T cell surface glycoprotein CD3 stimulants), HER2 antagonists(Receptor tyrosine-protein kinase erbB-2 antagonists)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Breast Cancer

Inactive Indication-

Originator Organization

Sanofi

Active Organization

Sanofi

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Chen, Liqing ; Li, Aiqun ; Nabel, Gary J ; Hebert, Andrew ; Kirby, Patrick ; Garrigou, Audrey ; Cortez-Retamozo, Virna ; Levit, Mikhail ; Poulton, Emma-Jane ; Xing, Zhen ; Zhang, Bailin ; Vicente, Rita ; Wu, Lan ; Wiederschain, Dmitri ; Rao, Ercole ; Song, Zhili ; Pao, Lily ; Qiu, Huawei ; Ospina, Beatriz ; Seung, Edward ; Deng, Gejing ; Sanicola-Nadel, Michele ; Yang, Zhi-Yong ; Beil, Christian ; Ulinski, Greg ; Bangari, Dinesh S ; Wei, Ronnie ; Piepenhagen, Peter

Effective antitumour immunity depends on the orchestration of potent T cell responses against malignancies¹. Regression of human cancers has been induced by immune checkpoint inhibitors, T cell engagers or chimeric antigen receptor T cell therapies^2-4. Although CD8 T cells function as key effectors of these responses, the role of CD4 T cells beyond their helper function has not been defined. Here we demonstrate that a trispecific antibody to HER2, CD3 and CD28 stimulates regression of breast cancers in a humanized mouse model through a mechanism involving CD4-dependent inhibition of tumour cell cycle progression. Although CD8 T cells directly mediated tumour lysis in vitro, CD4 T cells exerted antiproliferative effects by blocking cancer cell cycle progression at G1/S. Furthermore, when T cell subsets were adoptively transferred into a humanized breast cancer tumour mouse model, CD4 T cells alone inhibited HER2⁺ breast cancer growth in vivo. RNA microarray analysis revealed that CD4 T cells markedly decreased tumour cell cycle progression and proliferation, and also increased pro-inflammatory signalling pathways. Collectively, the trispecific antibody to HER2 induced T cell-dependent tumour regression through direct antitumour and indirect pro-inflammatory/immune effects driven by CD4 T cells.

100 Deals associated with Anti-HER2/CD3/CD28 trispecific antibody(Sanofi)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Preclinical	United States	Sanofi	23 Feb 2022

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Biosimilar

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