 A trispecific antibody targeting HER2 and T cells inhibits breast cancer growth via CD4 cellsEdward Seung,
Zhen Xing,
Lan Wu,
Ercole Rao,
Virna Cortez-Retamozo,
Beatriz Ospina,
Liqing Chen,
Christian Beil,
Zhili Song,
Bailin Zhang,
Mikhail Levit,
Gejing Deng,
Andrew Hebert,
Patrick Kirby,
Aiqun Li,
Emma-Jane Poulton,
Rita Vicente,
Audrey Garrigou,
Peter Piepenhagen,
Greg Ulinski,
Michele Sanicola-Nadel,
Dinesh S. Bangari,
Huawei Qiu,
Lily Pao (),
Dmitri Wiederschain,
Ronnie Wei,
Zhi-yong Yang () and
Gary J. Nabel ()
Nature, 2022, vol. 603, issue 7900, 328-334 Abstract: Abstract 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 therapies2–4. 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. Date: 2022 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:603:y:2022:i:7900:d:10.1038_s41586-022-04439-0 Ordering information: This journal article can be ordered from DOI: 10.1038/s41586-022-04439-0 Access Statistics for this article Nature is currently edited by Magdalena Skipper More articles in Nature from Nature |
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